6-amino substituted imidazo[4,5-bipyridines as angiotensin II antagonists

ABSTRACT

Substituted imidazo[4,5-b]pyridines of structural formula: ##STR1## are angiotensin II antagonists useful in the treatment of hypertension and congestive heart failure.

This is a continuation-in-part of copending application Ser. No. 516,286filed May 4, 1990 which is a continuation-in-part application ofcopending application Ser. No. 358,971 filed May 30, 1989, nowabandoned.

SUMMARY OF THE INVENTION

This invention relates to novel compounds of structural formula I whichare angiotensin II (AII) antagonists that inhibit the binding of AII tothe AT₁ and AT₂ receptor sites, useful in the treatment of hypertension,congestive heart failure, and elevated intraocular pressure.

It also relates to processes for preparing the novel compounds;pharmaceutical formulations comprising one or more of the compounds asactive ingredient; and, a method of treatment of hypertension,congestive heart failure, and elevated intraocular pressure.

BACKGROUND OF THE INVENTION

Renin-angiotensin system (RAS) plays a central role in the regulation ofnormal blood pressure and seems to be critically involved inhypertension development and maintenance as well as congestive heartfailure. Angiotensin II (AII), an octapeptide hormone is produced mainlyin the blood during the cleavage of angiotensin I by angiotensinconverting enzyme (ACE) localized on the endothelium of blood vessels oflung, kidney, and many other organs, and is the end product of the RAS.AII is a powerful arterial vasoconstricter that exerts its action byinteracting with specific receptors present on cell membranes. One ofthe possible modes of controlling the RAS is angiotensin II receptorantagonism. Several peptide analogs of A II are known to inhibit theeffect of this hormone by competitively blocking the receptors, buttheir experimental and clinical applications have been limited by thepartial agonist activity and lack of oral absorption [M. Antonaccio.Clin. Exp. Hypertens. A4, 27-46 (1982); D. H. P. Streeten and G. H.Anderson, Jr.--Handbook of Hypertension, Clinical Pharmacology ofAntihypertensive Drugs, ed. A. E. Doyle, Vol. 5, pp. 246-271, ElsevierScience Publisher, Amsterdam, The Netherlands, 1984].

Recently, several non-peptide compounds have been described as A IIantagonists. Illustrative of such compounds are those disclosed in U.S.Pat. Nos. 4,207,324; 4,340,598; 4,576,958; 4,582,847; and 4,880,804; inEuropean Patent Applications 028,834; 245,637; 253,310; and 291,969; andin articles by A. T. Chiu, et al. [Eur. J. Pharm. Exp. Therap, 157,13-21 (1988)] and by P. C. Wong, et al. [J. Pharm. Exp. Therap, 247, 1-7(1988)]. All of the U.S. Patents, European Patent Applications 028,834and 253,310 and the two articles disclose substituted imidazolecompounds which are generally bonded through a lower alkyl bridge to asubstituted phenyl. European Patent Application 245,637 disclosesderivatives of4,5,6,7-tetrahydro-2H-imidazo[4,5-c]-pyridine-6-carboxylic acid andanalogs thereof as antihypertensive agents.

Imidazo[4,5-b]pyridines have been disclosed by Merck & Co., I.C.I.,Takeda and Eisai in following European Patent Publications: 400,974;399,731; 434,038; 549,136 and 420,237, respectively. The compoundsdisclosed in the above-cited applications, with the exception of EP400,974, do not disclose 6-amino-3H-imidazo[4,5-b]pyridines bearing abiphenyl substituent substituted with a sulfonyl group. The compounds ofthe present invention are encompassed within the genus of EP 400,974,which is substantially the same as U.S. Ser. No. 07/516,286 filed on May5, 1990.

DETAILED DESCRIPTION OF THE INVENTION

This invention relates to 6-amino substituted imidazo[4,5-b]pyridines ofthe structural formula I shown below which are angiotensin IIantagonists and are useful in the treatment of hypertension, congestiveheart failure, and elevated intraocular pressure ##STR2## or apharmaceutically acceptable salt thereof wherein: R¹ is:

(a) --SO₂ NHC(O)R²³,

(b) --SO₂ NHC(O)NR⁴ R²³, or

(c) --SO₂ NHC(O)N[CH₂ CH₂ ]₂ O;

R^(2a) and R^(2b) are independently:

(a) H,

(b) Cl, Br, I, F,

(c) C₁ -C₆ -alkyl, substituted or unsubstituted with aryl, furyl,thienyl, pyridyl, C₃ -C₆ -cycloalkyl, F, C₁ -C₃ -alkoxy, polyfluoro-C₁-C₄ -alkyl, morpholine, pyrrolidine, and --N(R⁴)(R²³),

(d) C₁ -C₆ -alkoxy, unsubstituted or substituted with F andpolyfluoro-C₁ -C₄ -alkyl,

(e) C₁ -C₆ -alkoxyalkyl, or

(f) aryl;

wherein aryl is phenyl or naphthyl substituted or unsubstituted with oneor two substituents selected from the group consisting of Cl, Br, I, F,C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, CF₃, C₁ -C₄ -alkylthio, OH, NH(C₁ -C₄-alkyl), N(C₁ -C₄ -alkyl)₂, CO₂ H, and CO₂ -C₁ -C₄ -alkyl;

R⁴ is:

(a) H,

(b) aryl, wherein aryl is as defined above, or

(c) C₁ -C₆ -alkyl, substituted or unsubstituted with aryl, furyl,thienyl, pyridyl, C₃ -C₆ -cycloalkyl, and F;

R4a is:

(a) H,

(b) aryl, wherein aryl is as defined above, or

(c) C₁ -C₆ -alkyl, substituted or unsubstituted with aryl, furyl,thienyl, pyridyl, C₃ -C₆ -cycloalkyl, and F;

R⁵ is:

(a) --NH₂,

(b) --N(R⁴)R²³,

(c) --N(R⁴)COR²³,

(d) --N(R⁴)(C₃ -C₇ -cycloalkyl),

(e) ##STR3## (f) --NHSO₂ CF₃, (g) --NHSO₂ R²³,

(h) --NHSO₂ NHR²³,

(i) --NHSO₂ NHCOR²³,

(j) --NHSO₂ NHSO₂ R²³,

(k) --N(R⁴)CO₂ R²³,

(l) --N(R⁴)CON(R⁴)(R²³),

(m) ##STR4## (n) ##STR5## n is: 0, 1 or 2; Z is:

(a) (CH₂)n,

(b) NR⁴,

(c) NCOR²³,

(d) NCO₂ R²³,

(e) NSO₂ R²³, or

(f) O ;

R⁶ is:

(a) C₁ -C₉ -alkyl, C₂ -C₆ -alkenyl or C₂ -C₆ -alkynyl, which issubstituted or unsubstituted with a substituent selected from the groupconsisting of: aryl as defined above, C₃ -C₇ -cycloalkyl, Cl, Br, I, F,--CF₂ CF₃, --N(C₁ -C₄ -alkyl)₂, --CF₃, --CF₂ CH₃, C₁ -C₄ -alkoxy; or

(b) polyfluoro-C₁ -C₄ -alkyl,

(c) C₃ -C₇ -cycloalkyl, unsubstituted or substituted with one or twosubstituents selected from the group consisting of: C₁ -C₄ -alkyl or--CF₃ or

(d) C₁ -C₆ -alkyloxy;

R^(7a) and R^(7b) are independently:

(a) H,

(b) --C₁ -C₅ -alkyl,

(c) --C₁ -C₅ -polyfluoroalkyl,

(d) --C₃ -C₆ -cycloalkyl,

(e) Cl, Br, I, F,

(f) --O--C₁ -C₅ -alkyl,

(g) --S--C₁ -C₅ -alkyl,

(h) --CO₂ R⁴, or

(i) --CON(R⁴)(R²³);

R²³ is:

(a) aryl as defined above,

(b) heteroaryl as defined below,

(c) C₃ -C₆ -cycloalkyl,

(d) C₁ -C₇ -alkyl which can be optionally substituted with a substituentthat is a member selected from the group consisting of: aryl as definedabove, heteroaryl as defined above, --C₃ -C₇ -cycloalkyl, --O(C₃ -C₇-cycloalkyl) --OH, --SH, --C₁ -C₄ -alkyl, --O(C₁ -C₄ -alkyl), --S(C₁ -C₄-alkyl), --CF₃, Cl, Br, F, I, --CO₂ H, --CO₂ -C₁ -C₄ -alkyl, --NH₂,--NH(C₁ -C₄ -alkyl), --NHCOR^(4a), --N(C₁ -C₄ -alkyl)₂, and --OC₆ H₅ --or

(e) polyfluoro-C₁ -C₄ -alkyl; and

wherein heteroaryl is defined as a 5- or 6-membered aromatic ringcontaining 1, 2 or 3 heteroatoms selected from the group consisting ofO, N, and S.

The terms "alkyl," "alkenyl," "alkynyl," and the like include both thestraight chain and branched chain species of these generic terms whereinthe number of carbon atoms in the species permit. Unless otherwisenoted, the specific names for these generic terms shall mean thestraight chain species. For example, the term "butyl" shall means thenormal butyl substituent, n-butyl.

The heteroaryl substituent recited above represents any 5- or 6-memberedaromatic ring containing from one to three heteroatoms selected from thegroup consisting of nitrogen, oxygen, and sulfur, for example, pyridyl,thienyl, furyl, pyrazolyl, pyrrolyl, imidazolyl, pyridazinyl,pyrimidinyl, pyrazinyl, isoxazolyl, isothiazolyl, oxazolyl, triazolyland thiazolyl.

An embodiment of the novel compounds of this invention is the class ofcompounds of Formula II ##STR6## or a pharmaceutically acceptable saltthereof wherein: R¹ is:

(a) SO₂ NHCOR²³, or

(b) SO₂ NHCONR⁴ R²³ ;

R^(2a) is:

(a) H, or

(b) C₁ -C₆ -alkyl or C₁ -C₆ -alkoxy, unsubstituted or substituted withpolyfluoro-C₁ -C₆ -alkyl;

R⁵ is:

(a) -N(R⁴)COR²³,

(b) -NHSO₂ R²³,

(c) -N(R⁴)CO₂ R²³,

(d) -N(R⁴)CON(R⁴)R²³,

(e) ##STR7## (f) ##STR8## (g) ##STR9## n is 0, 1, or 2; Z is:

(a) 0,

(b) NCOR²³,

(c) NCO₂ R²³,

(d) NSO₂ R²³, or

(e) (CH₂)_(n) ;

R^(7a) and R^(7b) are independently:

(a) H,

(b) C₁ -C₅ -alkyl, or

(c) CO₂ R⁴ ;

and all other substituents are as defined above.

Tables A-F are subclasses of this embodiment, it should be understoodthat when (C5H9) and (C6H11) are used in the tables they representcyclopentyl and cyclohexyl, respectively, and are representativecompounds of the invention: ##STR10## wherein:

R^(7a) and R^(7b) are independently: H or CH₃ and all othersubstitutents are as defined below:

    __________________________________________________________________________    R.sup.6          NR.sup.4a R.sup.23 R.sup.4      R.sup.23a                    __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                      NHEt               H            (CH.sub.2).sub.2                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      NHEt               Me           (CH.sub.2).sub.3                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      NHEt               H            CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)            (CH.sub.2).sub.3 CH.sub.3                                                                      NHEt               H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                      NHEt               Me           CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                      NHEt               H            CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2          (CH.sub.2).sub.3 CH.sub.3                                                                      NHEt               H            CH.sub.2 O(C.sub.6                                                            H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                      NHEt               H            CH.sub.2 CH.sub.2                                                             -thiophene-2-yl              (CH.sub.2).sub.3 CH.sub.3                                                                      NHEt               H            C.sub.6 H.sub.5              (CH.sub.2).sub.3 CH.sub.3                                                                      NHEt               H            3,5-dimethylphenyl-1-yl      (CH.sub.2).sub.3 CH.sub.3                                                                      NHEt               H            3,5-bis(trifluoromethyl)-                                                     4                                                                             phenyl-1-yl                  (CH.sub.2).sub.2 CH.sub.3                                                                      NHEt               H            (CH.sub.2).sub.2                                                              CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      NHEt               Me           (CH.sub.2).sub.3                                                              CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      NHEt               H            CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)            (CH.sub.2).sub.2 CH.sub.3                                                                      NHEt               H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                      NHEt               Me           CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                      NHEt               H            CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2          (CH.sub.2).sub.2 CH.sub.3                                                                      NHEt               H            CH.sub.2 O(C.sub.6                                                            H.sub.5)                     (CH.sub.2).sub.2 CH.sub.3                                                                      NHEt               H            CH.sub.2 CH.sub.2                                                             -thiophene-2-yl              (CH.sub.2).sub.2 CH.sub.3                                                                      NHEt               H            C.sub.6 H.sub.5              (CH.sub.2).sub.2 CH.sub.3                                                                      NHEt               H            3,5-dimethylphenyl-1-yl      (CH.sub.2).sub.2 CH.sub.3                                                                      NHEt               H            3,5-bis(trifluoromethyl)-                                                     4                                                                             phenyl-1-yl                  (CH.sub.2).sub.3 CH.sub.3                                                                      NHPr               H            (CH.sub.2).sub.2                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      NHPr               Me           (CH.sub.2).sub.3                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      NHPr               H            CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)            (CH.sub.2).sub.3 CH.sub.3                                                                      NHPr               H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub. 3                                                                     NHPr               Me           CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                      NHPr               H            CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2          (CH.sub.2).sub.3 CH.sub.3                                                                      NHPr               H            CH.sub.2 O(C.sub.6                                                            H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                      NHPr               H            CH.sub.2 CH.sub.2                                                             -thiophene-2-yl              (CH.sub.2).sub.3 CH.sub.3                                                                      NHPr               H            C.sub.6 H.sub.5              (CH.sub.2).sub.3 CH.sub.3                                                                      NHPr               H            3,5-dimethylphenyl-1-yl      (CH.sub.2).sub.3 CH.sub.3                                                                      NHPr               H            3,5-bis(trifluoromethyl)-                                                     5                                                                             phenyl-1-yl                  (CH.sub.2).sub.2 CH.sub.3                                                                      NHPr               H            (CH.sub.2).sub.2                                                              CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      NHPr               Me           (CH.sub.2).sub.3                                                              CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      NHPr               H            CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9 )           (CH.sub.2).sub.2 CH.sub.3                                                                      NHPr               H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                      NHPr               Me           CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                      NHPr               H            CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2          (CH.sub.2).sub.2 CH.sub.3                                                                      NHPr               H            CH.sub.2 O(C.sub.6                                                            H.sub. 5)                    (CH.sub.2).sub.2 CH.sub.3                                                                      NHPr               H            CH.sub.2 CH.sub.2                                                             -thiophene-2-yl              (CH.sub.2).sub.2 CH.sub.3                                                                      NHPr               H            C.sub.6 C.sub.5              (CH.sub.2).sub.2 CH.sub.3                                                                      NHPr               H            3,5-dimethylphenyl-1-yl      (CH.sub.2).sub.2 CH.sub.3                                                                      NHPr               H            3,5-bis(trifluoromethyl)-                                                     .                                                                             phenyl-1-yl                  (CH.sub.2).sub.3 CH.sub.3                                                                      N(CH.sub.3)Pr      H            (CH.sub.2).sub.2                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      N(CH.sub.3)Pr      Me           (CH.sub.2).sub.3                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)            (CH.sub.2).sub.3 CH.sub.3                                                                      N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                      N(CH.sub.3)Pr      Me           CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                      N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2          (CH.sub.2).sub.3 CH.sub.3                                                                      N(CH.sub.3)Pr      H            CH.sub.2 O(C.sub.6                                                            H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                      N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             -thiophene-2-yl              (CH.sub.2).sub.3 CH.sub.3                                                                      N(CH.sub.3)Pr      H            C.sub.6 H.sub. 5             (CH.sub.2).sub.3 CH.sub.3                                                                      N(CH.sub.3)Pr      H            3,5-dimethylphenyl-1-yl      (CH.sub.2).sub.3 CH.sub.3                                                                      N(CH.sub.3)Pr      H            3,5-bis(trifluoromethyl)-                                                     phenyl-1-yl                  (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)Pr      H            (CH.sub.2).sub.2                                                              CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)Pr      Me           (CH.sub.2).sub.3                                                              CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)            (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)Pr      Me           CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2          (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)Pr      H            CH.sub.2 O(C.sub.6                                                            H.sub.5)                     (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             -thiophene-2-yl              (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)Pr      H            C.sub.6 H.sub.5              (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)Pr      H            3,5-dimethylphenyl-1-yl      (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)Pr      H            3,5-bis(trifluoromethyl)-                                                     phenyl-1-yl                  (CH.sub.2).sub.3 CH.sub.3                                                                      NH-iso-Pr          H            (CH.sub.2).sub.3                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      NH-iso-Pr          H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                      NH-iso-Pr          Me           (CH.sub.2).sub.3                                                              CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      NH-iso-Pr          H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                      NH-iso-Pr          H            CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                      N(CH.sub.3)-iso-Pr H            (CH.sub.2).sub.3                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      N(CH.sub.3)-iso-Pr H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)-iso-Pr Me           (CH.sub.2).sub.3                                                              CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)-iso-Pr H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                      N(CH.sub.3)-iso-Pr H            CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                      NH-iso-Pr          H            CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2           __________________________________________________________________________     ##STR11##     wherein:

R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined below:

    __________________________________________________________________________    R.sup.6                NR.sup.4a R.sup.23        NR.sup.4 R.sup.23a           __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                            NHEt                      NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                            NHEt                      NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.3 CH.sub.3                                                                            NHEt                      NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                            NHEt                      NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                            NHEt                      N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                            NHEt                      NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                            NHEt                      NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.2 CH.sub.3                                                                            NHEt                      NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                            NHEt                      NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.2 CH.sub.3                                                                            NHEt                      N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                            NHPr                      NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                            NHPr                      NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.3 CH.sub.3                                                                            NHPr                      NH(CH.sub.2).sub.2                                                            CH(CH.sub.3 ).sub.2          (CH.sub.2).sub.3 CH.sub.3                                                                            NHPr                      NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                            NHPr                      N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                            NHPr                      NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                            NHPr                      NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.2 CH.sub.3                                                                            NHPr                      NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                            NHPr                      NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.2 CH.sub.3                                                                            NHPr                      N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                            NH-iso-Pr                 NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                            NH-iso-Pr                 NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.3 CH.sub.3                                                                            NH-iso-Pr                 NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                            NH-iso-Pr                 NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                            NH-iso-Pr                 N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                            NH-iso-Pr                 NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                            NH-iso-Pr                 NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.2 CH.sub.3                                                                            NH-iso-Pr                 NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                            NH-iso-Pr                 NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.2 CH.sub.3                                                                            NH-iso-Pr                 N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.3 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.2 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.2 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        N(CH.sub.3 )CH.sub.2                                                          (C.sub.6 H.sub.5).           __________________________________________________________________________     ##STR12##     wherein:

R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined below:

    __________________________________________________________________________    R.sup.6          R.sup.23          R.sup.4       R.sup.23a                    __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             (CH.sub.2).sub.2                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             (CH.sub.2).sub.3                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       Me            (CH.sub.2).sub.3                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             (CH.sub.2).sub.4                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       Me            (CH.sub.2).sub.4                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             (CH.sub.2).sub.5                                                              CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CH(CH.sub.3).sub                                                     .2                           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CH(CH.sub.3)CH(C                                                     H.sub.3).sub.2               (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 (C.sub.5                                                             H.sub.9)                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 (C.sub.6                                                             H.sub.11)                    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.11)           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 (C.sub.6                                                             H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       Me            CH.sub.2 (C.sub.6                                                             H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       Me            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH(CH.sub.3)CH.sub.2                                                          CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH(CH.sub.3)CH.sub.2                                                          CH.sub.2 CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             C(CH.sub.3).sub.2                                                             CH.sub.2 CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             C(CH.sub.3).sub.2                                                             CH.sub.2 CH.sub.2                                                             CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CHC(CH.sub.3).sub.2          (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CHC(CH.sub.3).su                                                     b.2                          (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             OCH.sub.3                    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             O(C.sub.6 H.sub.5)           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             OCH.sub.2 CH.sub.3           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2          (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 OCH.sub.2                                                            CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub. 2 OCH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 OCH(CH.sub.3).su                                                     b.2                          (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 OCH.sub.2                                                            CH.sub.2 CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 OCH.sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 O(C.sub.6                                                            H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 O(C.sub.5                                                            H.sub.9)                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 OCH.sub.2                                                            CH.sub.2 OCH.sub.3           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             -furan-2-yl                  (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             -furan-3-yl                  (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             -thiophene-2-yl              (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub. 3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             -thiophene-3-yl              (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             cyclopropane                 (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             2,2-dimethylcyclo-                                                            propane-1-yl                 (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             C.sub.5 H.sub.9              (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             C.sub.6 H.sub.11             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             C.sub.6 H.sub.5              (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             2-CH.sub.3 --C.sub.6                                                          H.sub.4                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             2-CH.sub.3 --C.sub.6                                                          H.sub.4                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             2-CF.sub.3 --C.sub.6                                                          H.sub.4                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             3-CH.sub.3 --C.sub.6                                                          H.sub.4                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             3-CH.sub.2 CH.sub.2                                                           CH.sub.3 --C.sub.6                                                            H.sub.4                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             3-CF.sub.3 --C.sub.6                                                          H.sub.4                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             3,5-dimethylphenyl-1-yl      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             3,5-bis(trifluoro-                                                            methyl)phenyl-1-yl           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             furan-2-yl                   (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             furan-3-yl                   (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             thiophene-2-yl               (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             thiophene-3-yl               (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             3-methylthiophene-2-yl       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             3-chlorothiophene-2-yl       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             3-bromothiophene-2-yl        (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             3-methylfuran-2-yl           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             3-chlorofuran-2-yl           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             3-bromofuran-2-yl            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                       H             4-propylphenyl               (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             (CH.sub.2).sub.2                                                              CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             Butyl                        (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       Me            Butyl                        (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             .sup.n Pentyl                (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             .sup.n Hexyl                 (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH(CH.sub.3).sub                                                     .2                           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH(CH.sub.3)CH(C                                                     H.sub.3).sub.2               (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 (C.sub.5                                                             H.sub.9)                     (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       Me            CH.sub.2 CH.sub.2                                                             (C.sub. 5 H.sub.9)           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 (C.sub.6                                                             H.sub.11)                    (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.11)           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 (C.sub.6                                                             H.sub.5)                     (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH(CH.sub.3)CH.sub.2                                                          CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH(CH.sub.3)CH.sub.2                                                          CH.sub.2 CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             C(CH.sub.3).sub.2                                                             CH.sub.2 CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             C(CH.sub.3).sub.2                                                             CH.sub.2 CH.sub.2                                                             CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CHC(CH.sub.3).sub.2          (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CHC(CH.sub.3).su                                                     b.2                          (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             OCH.sub.3                    (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             O(C.sub.6 H.sub.5)           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             OCH.sub.2 CH.sub.3           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2          (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 OCH.sub.2                                                            CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 OCH.sub.2                                                            (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 OCH(CH.sub.3).su                                                     b.2                          (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 OCH.sub.2                                                            CH.sub.2 CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 OCH.sub.2                                                            CH(CH.sub.3).sub. 2          (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 O(C.sub.6                                                            H.sub.5)                     (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 O(C.sub.5                                                            H.sub.9)                     (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 OCH.sub.2                                                            CH.sub.2 OCH.sub.3           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             -furan-2-yl                  (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             -furan-3-yl                  (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             -thiophene-2-yl              (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             CH.sub.2 CH.sub.2                                                             -thiophene-3-yl              (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             cyclopropane                 (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             2,2-dimethylcyclo-                                                            propane-1-yl                 (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             C.sub.5 H.sub.9              (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             C.sub. 6 H.sub.11            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             C.sub.6 H.sub.5              (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             2-CH.sub.3 --C.sub.6                                                          H.sub.4                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             2-CH.sub.3 --C.sub.6                                                          H.sub.4                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             2-CF.sub.3 --C.sub.6                                                          H.sub.4                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             3-CH.sub.3 --C.sub.6                                                          H.sub.4                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             3-CH.sub.2 CH.sub.2                                                           CH.sub.3 --C.sub.6                                                            H.sub.4                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             3-CF.sub.3 --C.sub.6                                                          H.sub.4                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             3-CF.sub.3 -5-CF.sub.3                                                        --C.sub.6 H.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             furan-2-yl                   (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             furan-3-yl                   (CH.sub.2).sub.2 CH.sub. 3                                                                     (CH.sub.2).sub.2 CH.sub.3                                                                       H             thiophene-2-yl               (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             thiophene-3-yl               (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             3-methylthiophene-2-yl       (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             3-chlorothiophene-2-yl       (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             3-bromiothiophene-2-yl       (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             3-methylfuran-2-yl           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             3-chlorofuran-2-yl           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             3-bromofuran-2-yl            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       H             4-propylphenyl.              __________________________________________________________________________     ##STR13##     wherein:

R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined below:

    __________________________________________________________________________    R.sup.6          R.sup.23         R.sup.4a      NR.sup. R.sup.23a             __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            CH.sub.3                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH(CH.sub.2).sub.3                                                            CH.sub.3                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH(CH.sub.2).sub.4                                                            CH.sub.3                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NHCH.sub.2 CH(CH.sub.3).su                                                    b.2                           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NHC.sub.5 H.sub.9             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NHC.sub.6 H.sub.11            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NHC.sub.6 H.sub.5             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH(3,5-dimethylphen-1-yl)     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub. 2).sub.3 CH.sub.3                                                                     H             NHCH.sub.2 (C.sub.6                                                           H.sub.5)                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NHCH.sub.2 -thiophene-2-yl    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NHCH.sub.2 -thiophene-3-yl    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH.sub.2 (CH.sub.2).sub.2                                                     OCH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            OCH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             morpholine-1-yl               (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             N(CH.sub.3)(CH.sub.2).sub.                                                    3 CH.sub.3                    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             N(CH.sub.3)C.sub.6                                                            H.sub.5                       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            CH.sub.3                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2 ).sub.2 CH.sub.3                                                                     H             NH(CH.sub.2).sub.3                                                            CH.sub.3                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NH(CH.sub.2).sub.4                                                            CH.sub.3                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHCH.sub.2 CH(CH.sub.3).su                                                    b.2                           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHC.sub.5 H.sub.9             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHC.sub.6 H.sub.11            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHC.sub.6 H.sub.5             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NH(3,5-dimethylphen-1-yl)     (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHCH.sub.2 (C.sub.6                                                           H.sub.5)                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHCH.sub.2 -thiophene-2-yl    (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHCH.sub.2 -thiophene-3-yl    (CH.sub.2 ).sub.2 CH.sub.3                                                                     (CH.sub.2).sub.2 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            OCH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            OCH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             morpholine-1-yl               (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             N(CH.sub.3)(CH.sub.2).sub.                                                    2 CH.sub.3                    (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             N(CH.sub.3)C.sub.6                                                            H.sub.5                       (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5).            __________________________________________________________________________

                                      TABLE E                                     __________________________________________________________________________     ##STR14##                                                                    R.sup.6             NR.sup.4a R.sup.23   R.sup.7a         R.sup.7b            __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                         NHEt                 H                H                   (CH.sub.2).sub.3 CH.sub.3                                                                         NHEt                 H                CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                         NHEt                 CH.sub.3         H                   (CH.sub.2).sub.3 CH.sub.3                                                                         NHEt                 CH.sub.3         CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         NHEt                 H                H                   (CH.sub.2).sub.2 CH.sub.3                                                                         NHEt                 H                CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         NHEt                 CH.sub.3         H                   (CH.sub.2).sub.2 CH.sub.3                                                                         NHEt                 CH.sub.3         CH.sub.3            (CH.sub.2).sub.3 CH.sub. 3                                                                        NHPr                 H                H                   (CH.sub.2).sub.3 CH.sub.3                                                                         NHPr                 H                CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                         NHPr                 CH.sub.3         H                   (CH.sub.2).sub.3 CH.sub.3                                                                         NHPr                 CH.sub.3         CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         NHPr                 H                H                   (CH.sub.2).sub.2 CH.sub.3                                                                         NHPr                 H                CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         NHPr                 CH.sub.3         H                   (CH.sub.2).sub.2 CH.sub.3                                                                         NHPr                 CH.sub.3         CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                         NH-iso-Pr            H                H                   (CH.sub.2).sub.3 CH.sub.3                                                                         NH-iso-Pr            H                CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                         NH-iso-Pr            CH.sub.3         H                   (CH.sub.2).sub.3 CH.sub.3                                                                         NH-iso-Pr            CH.sub.3         CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         NH-iso-Pr            H                H                   (CH.sub.2).sub.2 CH.sub.3                                                                         NH-iso-Pr            H                CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         NH-iso-Pr            CH.sub.3         H                   (CH.sub.2).sub.2 CH.sub.3                                                                         NH-iso-Pr            CH.sub.3         CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr   H                H                   (CH.sub.2).sub.3 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr   H                CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr   CH.sub.3         H                   (CH.sub.2).sub.3 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr   CH.sub.3         CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr   H                H                   (CH.sub.2).sub.2 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr   H                CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr   CH.sub.3         H                   (CH.sub.2).sub.2 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr   CH.sub.3         CH.sub.3            __________________________________________________________________________

                  TABLE F                                                         ______________________________________                                         ##STR15##                                                                    ______________________________________                                    

wherein:

R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined below:

    __________________________________________________________________________    R.sup.6            R.sup.23        R.sup.4         R.sup.23a                  __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                        Bu              H               (CH.sub.2).sub.3                                                              CH.sub.3                   (CH.sub.2).sub.3 CH.sub.3                                                                        Bu              H               CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)          (CH.sub.2).sub.3 CH.sub.3                                                                        Bu              Me              (CH.sub.2).sub.3                                                              CH.sub.3                   (CH.sub.2).sub.3 CH.sub.3                                                                        Bu              H               CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)          (CH.sub.2).sub.3 CH.sub.3                                                                        Bu              H               CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2         (CH.sub.2).sub.2 CH.sub.3                                                                        Bu              H               (CH.sub.2).sub.3                                                              CH.sub.3                   (CH.sub.2).sub.2 CH.sub.3                                                                        Bu              H               CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)          (CH.sub.2).sub.2 CH.sub.3                                                                        Bu              Me              (CH.sub.2).sub.2                                                              CH.sub.3                   (CH.sub.2).sub.2 CH.sub.3                                                                        Bu              H               CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)          (CH.sub.2).sub.2 CH.sub.3                                                                        Bu              H               CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2.        __________________________________________________________________________

Another embodiment of this invention is the group of compounds ofFormula III ##STR16## or a pharmaceutically acceptable salt wherein: R¹is: -SO₂ NHCOR²³ or -SO₂ NHCONR⁴ R²³ ;

R^(2a) is: H, -CH₃, -CH₂ CH₃, -(CH₂)₂ CH₃, -CH(CH₃)₂, -CH₂ CH(CH₃)₂,-OCH₂ CH₃, or -OCH₂ CF₃ ;

R⁵ is:

--N(R⁴)COR²³,

--NHSO₂ R²³,

--N(R⁴)CO₂ R²³,

--N(R⁴)CON(R⁴)R²³, or ##STR17## R⁶ is: ethyl, propyl, butyl,cyclopropyl, ethyloxy or propyloxy.

                  TABLE G                                                         ______________________________________                                         ##STR18##                                                                    ______________________________________                                    

wherein:

R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined below:

    __________________________________________________________________________    R.sup.6           R.sup.23          R.sup.23a             R.sup.2a            __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                           Pr                  (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                       CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                 Pr                  (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                       CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.3                                                                Pr                  (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                       C.sub.6 H.sub.5       Pr                  (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                           Et                  (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                       CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                 Et                  (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                       CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.3                                                                Et                  (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                       C.sub.6 H.sub.5       Et                  (CH.sub.2).sub.2 CH.sub.3                                                                       (CH.sub.2).sub.2 CH.sub.3                                                                       CH.sub.2 CH.sub.2 (C.sub.6 H.sub.5)                                                                 Pr                  (CH.sub. 2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                       CH.sub.2 CH.sub.2 (C.sub.6 H.sub.5)                                                                 Et                  (CH.sub.2).sub.2 CH.sub.3                                                                       (CH.sub.2).sub.2 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                           Pr                  (CH.sub.2).sub.2 CH.sub.3                                                                       (CH.sub.2).sub.2 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                           Et                  (CH.sub.2).sub.2 CH.sub.3                                                                       (CH.sub.2).sub.2 CH.sub.3                                                                       C.sub.6 H.sub.5       Pr                  (CH.sub.2).sub.2 CH.sub.3                                                                       (CH.sub.2).sub.2 CH.sub.3                                                                       C.sub.6 H.sub.5       Et                  (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                       CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.3                                                                iso-Bu              (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                           iso-Bu              __________________________________________________________________________

                  TABLE H                                                         ______________________________________                                         ##STR19##                                                                    ______________________________________                                    

wherein:

R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined below:

    __________________________________________________________________________    R.sup.6             R.sup.23           R.sup.23a          R.sup.2a            __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                         (CH.sub.2).sub.3 CH.sub.3                                                                        (CH.sub.2).sub.3 CH.sub.3                                                                        Pr                  (CH.sub.2).sub.2 CH.sub.3                                                                         (CH.sub.2).sub.2 CH.sub.3                                                                        (CH.sub.2).sub.3 CH.sub.3                                                                        Pr                  (CH.sub.2).sub.3 CH.sub.3                                                                         (CH.sub.2).sub.3 CH.sub.3                                                                        (CH.sub.2).sub.3 CH.sub.3                                                                        Et                  (CH.sub.2).sub.2 CH.sub.3                                                                         (CH.sub.2).sub.2 CH.sub.3                                                                        (CH.sub.2).sub.3 CH.sub.3                                                                        Et                  (CH.sub.2).sub.2 CH.sub.3                                                                         (CH.sub.2).sub.2 CH.sub.3                                                                        (CH.sub.2).sub.3 CH.sub.3                                                                        iso-Bu.             __________________________________________________________________________

                  TABLE I                                                         ______________________________________                                         ##STR20##                                                                    ______________________________________                                    

wherein:

R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined below:

    __________________________________________________________________________    R.sup.6             R.sup.23         R.sup.23a            R.sup.2a            __________________________________________________________________________    CH.sub.2 CH.sub.3   Et               (CH.sub.2).sub.3 CH.sub.3                                                                          Pr                  CH.sub.2 CH.sub.3   CH.sub.3         CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                Pr                  (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                          Pr                  CH.sub.2 CH.sub.3   iso-Pr           CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                Pr                  (CH.sub.2).sub.2 CH.sub.3                                                                         iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                          Pr                  CH.sub.2 CH.sub.3   Et               (CH.sub.2).sub.3 CH.sub.3                                                                          Et                  CH.sub.2 CH.sub.3   CH.sub.3         CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                Et                  (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                          Et                  CH.sub.2 CH.sub.3   iso-Pr           CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                Et                  (CH.sub.2).sub.2 CH.sub.3                                                                         iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                          Et                  CH.sub.2 CH.sub.3   Et               (CH.sub.2).sub.3 CH.sub.3                                                                          iso-Bu              CH.sub.2 CH.sub.3   CH.sub.3         CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                iso-Bu              (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Pr           (CH.sub.2).sub.3 CH.sub.                                                                           iso-Bu              CH.sub.2 CH.sub.3   iso-Pr           CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                iso-Bu              (CH.sub.2).sub.2 CH.sub.3                                                                         iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                          iso-Bu.             __________________________________________________________________________

                  TABLE J                                                         ______________________________________                                         ##STR21##                                                                    ______________________________________                                    

wherein:

R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined below:

    __________________________________________________________________________    R.sup.6             R.sup.23          R.sup.23a           R.sup.2a            __________________________________________________________________________    (CH.sub.2).sub.2 CH.sub.3                                                                         Et                (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                  (CH.sub.2).sub.2 CH.sub.3                                                                         Et                (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                  CH.sub.2 CH.sub.3   Et                (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                  CH.sub.2 CH.sub.3   CH.sub.3          (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                  (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Pr            (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                  CH.sub.2 CH.sub.3   iso-Pr            (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                  (CH.sub.2).sub.2 CH.sub.3                                                                         Iso-Pr            (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                  (CH.sub.2).sub.2 CH.sub.3                                                                         Et                (CH.sub.2).sub.3 CH.sub.3                                                                         Et                  (CH.sub.2).sub.3 CH.sub.3                                                                         Et                (CH.sub.2).sub.3 CH.sub.3                                                                         Et                  CH.sub.2 CH.sub.3   Et                (CH.sub.2).sub.3 CH.sub.3                                                                         Et                  CH.sub.2 CH.sub.3   CH.sub.3          (CH.sub.2).sub.3 CH.sub.3                                                                         Et                  (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Pr            (CH.sub.2).sub.3 CH.sub.3                                                                         Et                  CH.sub.2 CH.sub.3   iso-Pr            (CH.sub.2).sub.3 CH.sub.3                                                                         Et                  (CH.sub.2).sub.2 CH.sub.3                                                                         iso-Pr            (CH.sub.2 ).sub.3 CH.sub.3                                                                        Et                  (CH.sub.2).sub.2 CH.sub.3                                                                         Et                (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu              (CH.sub.2).sub.2 CH.sub.3                                                                         Et                (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu              CH.sub.2 CH.sub.3   Et                (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu              CH.sub.2 CH.sub.3   CH.sub.3          (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu              (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Pr            (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu              CH.sub.2 CH.sub.3   iso-Pr            (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu              (CH.sub.2).sub.2 CH.sub.3                                                                         iso-Pr            (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu.             __________________________________________________________________________

The compounds of Formula (I) can be synthesized using the reactions andtechniques described herein below. The reactions are performed in asolvent appropriate to the reagents and materials employed and suitablefor the transformation being effected. It is understood by those skilledin the art of organic synthesis that the functionality present on theheterocycle and in the reactants being employed should be consistentwith the chemical transformations being conducted. Depending upon thereactions and techniques employed, optimal yields may require changingthe order of synthetic steps or use of protecting groups followed bydeprotection.

ABBREVIATIONS USED IN REACTION SCHEMES

    ______________________________________                                        Reagents:                                                                     ______________________________________                                        NBS              N-bromosuccinimide                                           AIBN             Azo(bis)isobutyronitrile                                     DDQ              Dichlorodicyanoquinone                                       Ac.sub.2 O       acetic anhydride                                             TEA              triethylamine                                                DMAP             4-dimethylaminopyridine                                      PPh.sub.3        triphenylphosphine                                           TFA              trifluoroacetic acid                                         TMS--Cl          trimethylsilyl chloride                                      Im               imidazole                                                    AcSK             potassium thioacetate                                        P-TsOH           p-toluenesulfonic acid                                       ______________________________________                                    

    ______________________________________                                        Solvents:                                                                     ______________________________________                                        Et.sub.2 O       diethyl ether                                                DMF              dimethylformamide                                            HOAc (AcOH)      acetic acid                                                  EtOAc (EtAc)     ethyl acetate                                                Hex              hexane                                                       THF              tetrahydrofuran                                              DMSO             dimethylsulfoxide                                            MeOH             methanol                                                     iPrOH            isopropanol                                                  DBU              1,8-diazabicyclo-[5.4.0]                                                      undec-7-ene                                                  Me.sub.3 SnCl    trimethylstannyl chloride                                    ______________________________________                                    

    ______________________________________                                        Others:                                                                       ______________________________________                                        rt              room temperature                                              TBDMS           t-butyldimethylsilyl                                          OTf             OSO.sub.2 CF.sub.3                                            OTs             OSO.sub.2 (4-methyl)phenyl                                    OMs             OSO.sub.2 CH.sub.3                                            Ph              phenyl                                                        FAB-MS (FABMS)  Fast atom bombardment mass                                    spectroscopy                                                                  NOE             Nuclear Overhauser Effect                                     SiO.sub.2       silica gel                                                    trityl          triphenylmethyl                                               ______________________________________                                    

As shown in Scheme 1, compounds of Formula I can be prepared by carryingout direct alkylation of alkali-metal salts of heterocycles (1) usingappropriately protected benzyl halide, tosylate (OTs) or mesylate (OMs)derivatives (2). The salt is prepared preferably using MH (where M islithium, sodium or potassium) is anhydrous dimethylformamide (DMF), orby treating it with a metal alkoxide such as sodium or potassiummethoxide, ethoxide or t-butoxide in an appropriate alcohol such asmethanol, ethanol or t-butanol as the solvent. The alkylation isgenerally carried out by dissolving the metal salt of the heterocycle ina dipolar aprotic solvent such as DMF or dimethylsulfoxide (DMSO) andreacting it with the alkylating agent at 20° C. to reflux temperature ofthe solvent for 1-24 hours. ##STR22## where Q=I, Br, Cl, -O-tosyl, or-O-mesyl.

If substituents and/or the hetero atom positions in the six-memberedring are not symetrically disposed, the alkylation on the imidazolenitrogen(s) generally produces a mixture of two regioisomers as productsarising from N¹ and N³ alkylation. These regioisomers I and Ia possessdistinct physico-chemical and biological properties and in most casescan be separated and purified by using conventional separationtechniques such as chromatography (flash column chromatography,medium-pressure liquid chromatography, high performance liquidchromatography) and/or crystallization. In those cases where separationof regioisomers is difficult by conventional techniques, the mixture canbe transformed into suitable derivatives that can be separated by theabove separation methods. The structural assignments of the isomers canbe made using Nuclear Overhauser Effect (NOE), ¹ H-¹³ C coupled NMRexperiments or X-ray crystallography.

When there is potential for alkylation on the R⁵, R^(7a), as R^(7b)substituents, this can be avoided by the use of suitable protectinggroups.

The heterocycles of type (1) can be prepared by any of the standardprocedures described in the literature [J. A. Montgomery and J. A.Secrist III in "Comprehensive Heterocyclic Chemistry," Vol. 5, A. R.Katritsky and C. W. Rees Eds., Pergamon Press 1984; pp 567-597 and631-656 and references cited therein]. As shown in Scheme 2, the mostwidely used starting materials: are the substituted 2,3-diaminopyridines(3). Fused imidazoles (4) can be prepared by condensation of (3) with anappropriate carboxylic acid, nitrile, imidate ester, or orthoesters,either neat, or in a solvent appropriate and compatible with thestarting materials and reagents, such as polyphosphoric acid, ethanol,methanol, hydrocarbon solvents, and with a catalytic amount of acid ifrequired. ##STR23## W=H or R⁶ CO ^(a) Alternate reagents and reactionconditions:

R⁶ C.tbd.N, PPA OC₂ H₅

R⁶ -C═NH•HCl, C₂ H₅ OH, Δ

R⁶ C(OCH₃)₃, toluene, H⁺, Δ

R⁶ CHO, C₂ H₅ OH, Cu(OCOCH₃)₂.

A preferred method for preparing heterocycles of type 13 are shown inSchemes 3 and 4. Nitration of an appropriately substituted2-amino-3-nitropyridine using nitric acid in sulfuric acid gives2-amino-3,5-dinitropyridine derivative 6. Treatment of 6 under reducingconditions such as H₂ with a catalyst such as Raney-Nickel or palladiumon carbon gives the 2,3,5-triaminopyridine derivative 7. Triamine 7 maybe handled as the salt of an inorganic acid such as HCl or H₃ PO₄. Thesalt may is preferrentially prepared by the addition of the inorganicacid directly to the reduction step reaction mixture immediately afterremoval of the catalyst by vacuum filtration. Heating the triamine with2 equivalents of an appropriate carboxylic acid in polyphosphoric acidprovides 6-amidoimidazopyridine 8. Alternatively, this transformationmay be performed using 2 equivalents of an appropriate acid chloridefollowed by heating in an aprotic solvent. The amide 8 may be hydrolysedto amine 9 by treatment with acid in water or alcoholic solvent.Treatment of amine 9 with an acid chloride provides analogs of 8,wherein R²³ is not equal to R⁶. Additionally, treatment of amine 9 withan isocyanate or an alkylcarbamyl chloride in the presence of baseaffords the urea analog 10.

Imidazopyridines bearing an alkoxy group at the 2-position may beprepared as shown in Scheme 4. Heating triaminopyridine analogs 7 in thepresence of excess tetraalkyl orthocarbonate affords imidazopyridinesbearing a 6-carbamate substituent 11. Imidazopyridine analogs bearing6-amino, 6-amido, and 6-ureido substituent are readily available from 11by using the transformations outlined in the scheme. ##STR24##

The biaryl sulfonamides 16 can be prepared using palladium(0) catalyzedcross-coupling reactions of appropriate aryl-organotin precursors [J. K.Stille, Pure Appl. Chem., 57, 1771 (1985); T. R. Baiely, Tetra Lett.,27, 4407 (1986); D. A. Widdowson and Y. Z. Zhang, Tetrahedron, 42, 2111(1986)], as outlined in Scheme 5. The organotin compound 13 [S. M.Moerlein, J. Organometallic Chem., 319, 29 (1987)], obtained from thearomatic precursor 12, may be coupled with the aryl sulfonamide 14 usingPd(PPh₃)₄ or (PPh₃)₂ PdCl₂ as catalysts to give the biaryl sulfonamide16. Benzylic bromination of 16 affords bromide 17. Similarly, the benzylbromide 23 may be prepared from the appropriate organotin precursor 20using the Pd(0) catalyzed cross-coupling reaction as outlined in Scheme6.

Substituted imidazopyridines 25 are preferentially prepared by reactionof the heterocycle 24 with benzyl bromide 23 in the presence of base asoutlined in Scheme 7. The t-butylsulfonamide 25 is deprotected usingtrifluoroacetic acid to form sulfonamide 26. Sulfonyl urea analogs 27may be prepared by treatment of sulfonamide 26 with alkyl isocyanates ordialkylcarbamyl chlorides. Acylsulfonamide analogs 28 are prepared fromintermediate sulfonamide 26 by treatment with an acyl chloride or anactivated ester such as one derived from a carboxylic acid and carbonyldiimidazole. ##STR25##

Chemical manipulation of the imidazopyridine-6-substituent may beperformed at the unsubstituted stage (R⁵⁰ ═H) or at the 3-substitutedstage of 29 as shown in Scheme 8. ##STR26##

It will be appreciated by those skilled in the art that functional grouptransformations can be conducted on aryl and heterocyclic rings toafford desired analogs. For example, esters may be converted to amidesby heating them with amines and an amide nitrogen if present in theheterocycle may be alkylated using bases such as sodium hydride in DMFwith the appropriate alkyl halide. Functional group protectionthroughout these syntheses will be chosen to be compatible withsubsequent reaction conditions. Ultimately such protecting groups willbe removed to generate the desired optimally active compounds of FormulaI.

The compounds of this invention form salts with various inorganic andorganic acids and bases which are also within the scope of theinvention. Such salts include ammonium salts, alkali metal salts likesodium and potassium salts, alkaline earth metal salts like the calciumand magnesium salts, salts with organic bases; e.g., dicyclohexylaminesalts, N-methyl-D-glucamine, salts with amino acids like arginine,lysine, and the like. Also, salts with organic and inorganic acids maybe prepared; e.g., HCl, HBr, H₂ SO₄, H₃ PO₄, methane-sulfonic,toluene-sulfonic, maleic, fumaric, camphorsulfonic. The non-toxic,physiologically, acceptable salts are preferred, although other saltsare also useful; e.g., in isolating or purifying the product.

The salts can be formed by conventional means such as by reacting thefree acid or free base forms of the product with one or more equivalentsof the appropriate base or acid in a solvent or medium in which the saltis insoluble, or in a solvent such as water which is then removed invacuo or by freeze-drying or by exchanging the cations of an existingsalt for another cation on a suitable ion exchange resin.

Angiotensin II (AII) is a powerful arterial vasoconstrictor, and itexerts its action by interacting with specific receptors present on cellmembranes. The compounds described in the present invention act ascompetitive antagonists of AII at the AT₁ and AT₂ receptors. In order toidentify AII antagonists and determine their efficacy in vitro, thefollowing ligand-receptor binding assays were used along with bindingassays reported in the literature (R. S. Chang et al, Biochem. Biophys.Res. Commun. 1990, 171, 813.).

Receptor binding assay using rabbit aortae membrane preparation

Three frozen rabbit aortae (obtained from Pel-Freeze Biologicals) weresuspended in 5 mM Tris-0.25M Sucrose, pH 7.4 buffer (50 ml) homogenized,and then centrifuged. The mixture was filtered through a cheesecloth andthe supernatant was centrifuged for 30 minutes at 20,000 rpm at 4° C.The pellet thus obtained was resuspended in 30 ml of 50 mM Tris-5 mMMgCl₂ buffer containing 0.2 mg/ml Bacitration and the suspension wasused for 100 assay tubes. Samples tested for screening were done induplicate. To the membrane preparation (0.25 ml) there was added ¹²⁵I-Sar¹ Ile⁸ -angiotensin II [obtained from New England Nuclear] (10 ul;20,000 cpm) with or without the test sample and the mixture wasincubated at 37° C. for 90 minutes. The mixture was then diluted withice-cold 50 mM Tris-0.9% NaCl, pH 7.4 (4 ml) and filtered through aglass fiber filter (GF/B Whatman 2.4" diameter). The filter was soakedin scintillation cocktail (10 ml) and counted for radioactivity usingPackard 2660 Tricarb liquid scintillation counter. The inhibitoryconcentration (IC₅₀) of potential AII antagonist which gives 50%displacement of the total specifically bound ¹²⁵ I-Sar¹ Ile⁸-angiotensin II was presented as a measure of the efficacy of suchcompounds as AII antagonists.

Receptor assay using Bovine adrenal cortex preparation

Bovine adrenal cortex was selected as the source of AII receptor.Weighed tissue (0.1 g is needed for 100 assay tubes) was suspended inTris.HCl (50 mM), pH 7.7 buffer and homogenized. The homogenate wascentrifuged at 20,000 rpm for 15 minutes. Supernatant was discarded andpellets resuspended in buffer [Na₂ HPO₄ (10 mM)-NaCl (120 mM)-disodiumEDTA (5 mM) containing phenylmethane sulfonyl fluoride (PMSF)(0.1 mM)].(For screening of compounds, generally duplicates of tubes are used). Tothe membrane preparation (0.5 ml) there was added 3H-angiotensin II (50mM) (10 ul) with or without the test sample and the mixture wasincubated at 37° C. for 1 hour. The mixture was then diluted with Trisbuffer (4 ml) and filtered through a glass fiber filter (GF/B Whatman2.4" diameter). The filter was soaked in scintillation cocktail (10 ml)and counted for radioactivity using Packard 2660 Tricarb liquidscintillation counter. The inhibitory concentration (IC₅₀) of potentialAII antagonist which gives 50% displacement of the total specificallybound ³ H-angiotensin II was presented as a measure of the efficacy ofsuch compounds as AII antagonists.

Receptor assay using rat brain membrane preparation

Membranes from rat brain (thalamus, hypothamus and midbrain) areprepared by homogenization in 50 mM Tris HCl (pH 7.4), and centrifugedat 50,000× g. The resulting pellets are washed twice in 100 mM NaCl, 5mM Na₂ •EDTA, 10 mM Na₂ HPO₄ (pH 7.4) and 0.1 mM PMSF by resuspensionand centrifugation. For binding assays, the pellets are resuspended in160 volumes of binding assay buffer (100 mM NaCl, 10 mM Na₂ HPO₄, 5 mMNa₂ •EDTA, pH 7.4, 0.1 mM PMSF, 0.2 mg/ml soybean trypsin inhibitor,0.018 mg/ml o-phenanthroline, 77 mg/ml dithiothreitol and 0.14 mg/mlbacitracin. For ¹²⁵ I.Ile⁸ -angiotensin II binding assays, 10 μl ofsolvent (for total binding), Sar¹,Ile⁸ -angiotensin II (1 μM) (fornonspecific binding) or test compounds (for displacement) and 10 μl of[¹²⁵ I]Sar¹,Ile⁸ -angiotensin II (23-46 pM) are added to duplicatetubes. The receptor membrane preparation (500 μl) is added to each tubeto initiate the binding reaction. The reaction mixtures are incubated at37° C. for 90 minutes. The reaction is then terminated by filtrationunder reduced pressure through glass-fiber GF/B filters and washedimmediately 4 times with 4 ml of 5 mM ice-cold Tris HCl (pH 7.6)containing 0.15M NaCl. The radioactivity trapped on the filters iscounted using a gamma counter.

The antihypertensive effects of the compounds described in the presentinvention may be evaluated using the methodology described below: MaleCharles River Sprague-Dawley rats (300-375 gm) were anesthetized withmethohexital (Brevital; 50 mg/kg i.p.) and the trachea was cannulatedwith PE 205 tubing. A stainless steel pithing rod (1.5 mm thick, 150 mmlong) was inserted into the orbit of the right eye and down th spinalcolumn. The rats were immediately placed on a Harvard Rodent Ventilator(rate-60 strokes per minute, volumn-1.1 cc per 100 grams body weight).The right carotid artery was ligated, both left and right vagal nerveswere cut, and the left carotid artery was cannulated with PE 50 tubingfor drug administration, and body temperature was maintained at 37° C.by a thermostatically controlled heating pad which received input from arectal temperature probe. Atropine (1 mg/kg i.v.) was then administered,and 15 minutes later propranolol (1 mg/kg i.v.). Thirty minutes laterangiotensin II or other agonists were administered intravenously at30-minute intervals and the increase in the diastolic blood pressure wasrecorded before and after drug or vehicle administration.

Using the methodology described above, representative compounds of thisinvention were evaluated and were found to exhibit an activity of atleast IC₅₀ <50 μM, in both the AT₁ and AT₂ angiotensin II receptorsubtypes, thereby demonstrating and confirming the utility of thecompounds of the invention as effective A II antagonists.

The compounds of the invention are useful in treating hypertension. Theyare also of value in the management of acute and chronic congestiveheart failure. These compounds may also be expected to be useful in thetreatment of secondary hyperaldosteronism, primary and secondarypulmonary hyperaldosteronism, primary and secondary pulmonaryhypertension, renal failure such as diabetic nephropathy,glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria ofprimary renal disease, end stage renal disease, renal transplanttherapy, and the like, renal vascular hypertension, left ventriculardysfunction, diabetic retinopathy and in the management of vasculardisorders such as migraine, Raynaud's disease, luminal hyperclasia, andto minimize the atherosclerotic process. The application of thecompounds of this invention for these and similar disorders will beapparent to those skilled in the art.

The compounds of this invention are also useful to treat elevatedintraocular pressure and to enhance retinal blood flow and can beadministered to patients in need of such treatment with typicalpharmaceutical formulations such as tablets, capsules, injectables andthe like as well as topical ocular formulations in the form ofsolutions, ointments, inserts, gels, and the like. Pharmaceuticalformulations prepared to treat intraocular pressure would typicallycontain about 0.1% to 15% by weight, preferably 0.5% to 2% by weight, ofa compound of this invention.

In the management of hypertension and the clinical conditions notedabove, the compounds of this invention may be utilized in compositionssuch as tablets, capsules or elixirs for oral administration,suppositories for rectal administration, sterile solutions orsuspensions for parenteral or intramuscular administration, and thelike. The compounds of this invention can be administered to patients(animals and human) in need of such treatment in dosages that willprovide optimal pharmaceutical efficacy. Although the dose will varyfrom patient to patient depending upon the nature and severity ofdisease, the patient's weight, special diets then being followed by apatient, concurrent medication, and other factors which those skilled inthe art will recognize, the dosage range will generally be about 1 to1000 mg. per patient per day which can be administered in single ormultiple doses. Perferably, the dosage range will be about 2.5 to 250mg. per patient per day; more preferably about 5 to 150 mg. per patientper day.

The compounds of this invention can also be administered in combinationwith other antihypertensives and/or diuretics and/or angiotensinconverting enzyme inhibitors and/or calcium channel blockers. Forexample, the compounds of this invention can be given in combinationwith such compounds as amiloride, atenolol, bendroflumethiazide,chlorothalidone, chlorothiazide, clonidine, cryptenamine acetates andcryptenamine tannates, deserpidine, diazoxide, guanethidene sulfate,hydralazine hydrochloride, hydrochlorothiazide, metolazone, metoprololtartate, methyclothiazide, methyldopa, methyldopate hydrochloride,minoxidil, pargyline hydrochloride, polythiazide, prazosin, propranolol,rauwolfia serpentina, rescinnamine, reserpine, sodium nitroprusside,spironolactone, timolol maleate, trichlormethiazide, trimethophancamsylate, benzthiazide, quinethazone, ticrynafan, triamterene,acetazolamide, aminophylline, cyclothiazide, ethacrynic acid,furosemide, merethoxylline procaine, sodium ethacrynate, captopril,delapril hydrochloride, enalapril, enalaprilat, fosinopril sodium,lisinopril, pentopril, quinapril hydrochloride, ramapril, teprotide,zofenopril calcium, diflusinal, diltiazem, felodipine, nicardipine,nifedipine, niludipine, nimodipine, nisoldipine, nitrendipine, and thelike, as well as admixtures and combinations thereof.

Typically, the individual daily dosages for these combinations can rangefrom about one-fifth of the minimally recommended clinical dosages tothe maximum recommended levels for the entities when they are givensingly.

To illustrate these combinations, one of the angiotensin II antagonistsof this invention effective clinically in the 2.5-250 milligrams per dayrange can be effectively combined at levels at the 0.5-250 milligramsper day range with the following compounds at the indicated per day doserange: hydrochlorothiazide (15-200 mg) chlorothiazide (125-2000 mg),ethacrynic acid (15-200 mg), amiloride (5-20 mg), furosemide (5-80 mg),propranolol (20-480 mg), timolol maleate (5-60 mg.), methyldopa (65-2000mg), felodipine (5-60 mg), nifedipine (5-60 mg), and nitrendipine (5-60mg). In addition, triple drug combinations of hydrochlorothiazide(15-200 mg) plus amiloride (5-20 mg) plus angiotensin II antagonist ofthis invention (3-200 mg) or hydrochlorothiazide (15-200 mg) plustimolol maleate (5-60) plus an angiotensin II antagonist of thisinvention (0.5-250 mg) or hydrochlorothiazide (15-200 mg) and nifedipine(5-60 mg) plus an angiotensin II antagonist of this invention (0.5-250mg) are effective combinations to control blood pressure in hypertensivepatients. Naturally, these dose ranges can be adjusted on a unit basisas necessary to permit divided daily dosage and, as noted above, thedose will vary depending on the nature and severity of the disease,weight of patient, special diets and other factors.

Typically, these combinations can be formulated into pharmaceuticalcompositions as discussed below.

About 1 to 100 mg. of compound or mixture of compounds of Formula I or aphysiologically acceptable salt is compounded with a physiologicallyacceptable vehicle, carrier, excipient, binder, preservative,stabilizer, flavor, etc., in a unit dosage form as called for byaccepted pharmaceutical practice. The amount of active substance inthese compositions or preparations is such that a suitable dosage in therange indicated is obtained.

Illustrative of the adjuvants which can be incorporated in tablets,capsules and the like are the following: a binder such as gumtragacanth, acacia, corn starch or gelatin; an excipient such asmicrocrystalline cellulose; a disintegrating agent such as corn starch,pregelatinized starch, alginic acid and the like; a lubricant such asmagnesium stearate; a sweetening agent such as sucrose, lactose orsaccharin; a flavoring agent such as peppermint, oil of wintergreen orcherry. When the unit dosage unitform is a capsule, it may contain, inaddition to materials of the above type, a liquid carrier such as fattyoil. Various other materials may be present as coatings or to otherwisemodify the physical form of the dosage unit. For instance, tablets maybe coated with shellac, sugar or both. A syrup or elixir may contain theactive compound, sucrose as a sweetening agent, methyl and propylparabens as preservatives, a dye and a flavoring such as cherry ororange flavor.

Sterile compositions for injection can be formulated according toconventional pharmaceutical practice by dissolving or suspending theactive substance in a vehicle such as water for injection, a naturallyoccuring vegetable oil like sesame oil, coconut oil, peanut oil,cottonseed oil, etc., or a synthetic fatty vehicle like ethyl oleate orthe like. Buffers, preservatives, antioxidants and the like can beincorporated as required.

The following examples further illustrate the preparation of thecompounds of Formula I and their incorporation into pharmaceuticalcompositions and, as such, are not be considered or construed aslimiting the invention recited in the appended claims.

Example 12-butyl-3-[[2'-[[(3-cyclopentyl-1-oxopropyl)amino]-sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxopentyl)-amino]-3H-imidazo[4,5-b]pyridine

Step 1: Preparation of 2-amino-3,5-dinitropyridine

To a stirred solution of 2-amino-3-nitropyridine (8.74 g, 63 mmol) inconc. H₂ SO₄ (50 mL) at 0° C. was added HNO₃ (3.10 mL, d=1.49) drop-wiseover 10 min. The mixture was warmed to r.t. for 20 min then heated to50° C. for 90 min. The reaction mixture was cooled and poured into 400 gof ice. The resulting precipitate was filtered, washed with cold water,and air dried to give 2-amino-3,5-dinitropyridine as a yellow solid.

Step 2: Preparation of2-butyl-6-[(1-oxopentyl)amino]-imidazo[4,5-b]pyridine

A mixture of 2-amino-3,5-dinitropyridine (5.32 g, 28.9 mmol), THF (100mL), methanol (250 mL) and Raney-nickel (3 mL of a 1:1 suspension in H₂O) was stirred under H₂ (1 atm.) was stirred for 5 h. The reactionmixture was quickly filtered into a receiving flask containing 5 mL ofconc. HCl and the solvent was removed in vacuo at r. t. To this crude2,3,5-triaminopyridine.HCl was added valeric acid (9.43 mL, 86.7 mmol)and polyphosphoric acid (100 mL) and this mixture was heated to 95° C.for 6 h. The warmed mixture was poured into stirred ice-H₂ O (200 mL)and this mixture was cooled and neutralized (to pH 4) by the addition ofconc. NH₄ OH. Extraction with EtOAc(3×75 mL), concentration, andpurification (SiO₂, 5% MeOH/EtOAc) gave the title compound as solid.

Step 3: Preparation of2-butyl-3-[[2'-[[(1,1-dimethyl-ethyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]-methyl]-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

A solution of 2-butyl-6-[(1-oxopentyl)amino]-imidazo[4,5-b]pyridine, K₂CO₃ (956 mg, 6.92 mmol), and4'-bromomethylbiphenyl-2-tert-butylsulfonamide 1.65 g, 3.46 mmol) in DMF(15 mL) was stirred for 12 h at r.t. The reaction mixture was pouredinto H₂ O (50 mL), extracted with EtOAc (2×50 mL), concentrated, andpurified (SiO₂, 4:1 EtOAc/hexanes) to give the title compound as a foam.

Step 4: Preparation of2-butyl-3-[[2'-[aminosulfonyl]-[1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxopentyl)-amino]-3H-imidazo[4,5-b]pyridine

A solution of2-butyl-3-[[2'-[[(1,1-dimethyl-ethyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine(710 mg, 1.23 mmol) in trifluoroacetic acid (50 mL) was stirred at r. t.for 12 h. The mixture was concentrated, dissolved in EtOAc (40 mL) andwashed with saturated aqueous Na₂ CO₃. The organic extracts were dried(K₂ CO₃) and concentrated to give the title compound as a solid.

Step 5: Preparation of2-butyl-3-[[2'-[[(3-cyclopentyl-1-oxopropyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxopentyl)-amino]-3H-imidazo-[4,5-b]pyridine

To a mixture of2-butyl-3-[[2'-[[aminosulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxopentyl)-amino]-3H-imidazo[4,5-b]-pyridine(88 mg, 0.169 mmol in pyridine (2.0 mL) was added 3-cyclopentylpropionylchloride (0.10 mL). After 12 h at r. t., MeOH (2 mL) was added and themixture was concentrated, dissolved in EtOAc (40 mL), washedsequentially with H₂ O (15 mL) and brine (15 mL), concentrated, andpurified (SiO₂, (90; 9:1 CH₂ Cl₂ /MeOH/NH₄ OH) to give the titlecompound as a solid.

¹ H NMR (200 MHz, 1:1 CDCl3/CD₃ OD) d 8.52 (d, 1H, J=2 Hz), 8.24 (d, 1H,J=2 Hz) 8.14 (dd, 1H, J=1.4 and 7.8 Hz), 7.55-7.39 (m, 2H), 7.32 (d, 2H,J=9 Hz), 7.18 (dd, 1H, J=1.4 and 6.0 Hz), 7.10 (d, 2H, J=9 Hz), 5.52 (s,2H), 2.89 (t, 2H, J=7.4 Hz) 2.40 (t, 2H, J=7.2 Hz), 1.89-1.25 (m, 21H),0.98-0.80 (m, 6H).

Example 2

The potassium salt of this AII antagonist and the other AII antagonistsdescribed in the examples were prepared by treatment with one molarequivalent of KOH in CH₃ OH.

2-butyl-3-[[2'-[[(1-oxohexyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxopentyl)amino]-3H-imidazo]4,5-b]pyridine

2-Butyl-3-[[2'-[aminosulfonyl][1,1'-biphenyl]-4-yl]-methyl]-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]-pyridine(85 mg, 0.162 mmol in pyridine (2.0 mL) was added hexanoyl chloride(0.23 mL). After 12 h at r. t., MeOH (2 mL) was added and the mixturewas concentrated, dissolved in EtOAc (40 mL), washed sequentially withH₂ O (15 mL) and brine (15 mL), concentrated, and purified (SiO₂,(93:3:4 CH₂ Cl₂ /MeOH/HOAc) to give the title compound as a solid.

¹ H NMR (200 MHz, 1:1 CDCl₃ /CD₃ OD) d 8.55 (s, 1H, b), 8.21 (s, 1H, b),8.19 (d, 1H) 7.62-7.43 (m, 2H), 7.30-7.15 (m, 3H) 7.15-7.03 (m, 2H) 5.52(s, 2H), 2.87 (t, 2H) 2.38 (t, 2H), 1.90-0.80 (m, 25H).

Example 32-butyl-3-[[2'[[[(butylamino)carbonyl]amino]sulfonyl]-[1,1'-biphenyl]-4-yl]methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

To a mixture of2-butyl-3-[[2'-[aminosulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxopentyl)-amino]-3H-imidazo[4,5-b]-pyridine(59 mg, 0.113 mmol in DMF (0.3 mL) and triethylamine (0.3 mL) was addedbutylisocyanate (0.038 mL). After heating to 60° C. for 12 h, themixture was cooled to r.t. and CH₂ Cl₂ (50 mL) was added. Sequentialwashing with 5% aqueous citric acid (25 mL), and brine and evaporationof the organic layer gave a crude product which was further purified(SiO₂, (96:1.5:2 CH₂ Cl₂ /MeOH/HOAc) to give the title compound as asolid.

¹ H NMR (200 MHz, 1:1 CDCl₃ /CD₃ OD) d 8.54 (s, 1H, b), 8.23 (s, 1H, b),8.10 (d, 1H) 7.60-7.38 (m, 2H), 7.35-7.15 (m, 3H) 7.09 (d, 2H) 5.52 (s,2H), 2.97-2.76 (m, 4H) 2.39 (t, 2H), 1.85-1.59 (m, 4H) 1.50-1.03 (m, 8H)1.00-0.72 (m, 9H).

Example 42-butyl-3-[[2'-[[(2,2-diphenyl-1-oxoethyl)amino]-sulfonyl][1,1'-biphenyl]-4-yl]methyl]-7-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

Step 1: Preparation of 2-amino-4-methyl-3,5-dinitro-pyridine

To a stirred solution of 2-amino-4-methyl-3-nitropyridine (25.6 g, 167mmol) in conc. H₂ SO₄ (50 mL) at 0° C. was added HNO₃ (7.77 mL, d=1.49)drop-wise over 30 min. The mixture was warmed to r.t. for 1 h thenheated to 50° C. for 60 min. The reaction mixture was cooled and pouredinto 500 g of ice. The resulting precipitate was filtered, washed with50 mL of H₂ O, and air dried to give2-amino-4-methyl-3,5-dinitro-pyridine as a yellow solid.

Step 2: Preparation of6-[(1-oxopentyl)amino]-2-butyl-7-methylimidazo[4,5-b]pyridine

The title compound was prepared from2-amino-4-methyl-3,5-dinitropyridine by a method similar to thatdescribed in Example 1, Step 2.

Step 3: Preparation of2-butyl-3-[[2'-[[(1,1-dimethylethyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-7-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

The title compound was prepared from6-[(1-oxopentyl)amino]-2-butyl-7-methylimidazo[4,5-b]-pyridine asdescribed in Example 1, Step 3.

Step 4: Preparation of2-butyl-3-[[2'-[(amino)-sulfonyl][1,1'-biphenyl]-4-yl]methyl]-7-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

The title compound was prepared from2-Butyl-3-[[2'-[[(1,1-dimethylethyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-7-methyl-6-[(1-oxopentyl)-amino]-3H-imidazo[4,5-b]pyridineas described in Example 1, Step 4.

Step 5: Preparation of2-butyl-3-[[2'-[[(2,2-diphenyl-1-oxoethyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-7-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

The title compound was prepared from2-butyl-3-[[2'-[(amino)sulfonyl][1,1'-biphenyl]-4-yl]methyl]-7-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridineand diphenylacetyl chloride as described in Example 1, Step 5.

¹ H NMR (200 MHz, 1:1 CDCl₃ /CD₃ OD) d 8.25 (s, 1H), 8.20 (d, 1H)7.55-7.38 (m, 3H), 7.15-6.70 (m, 14H), 5.52 (s, 2H), 4.49 (s, 1H), 2.86(t, 2H), 2.55 (s, 3H), 2.41 (t, 2H), 1.81-1.60 (m, 4H) 1.52-1.30 (m, 4H)1.03-0.85 (m, 6H).

Example 52-butyl-3-[[2'-[[(1-oxopentyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

Step 1: Preparation of 2-amino-6-methyl-3,5-dinitropyridine

To a stirred solution of 2-amino-6-methylpyridine (38 g, 352 mmol) inconc. H₂ SO₄ (70 mL) at 0 ° C. was added HNO₃ (16.5 mL, d=1.49)drop-wise over 30 min. The mixture was warmed stirred an additional 1 hat 0° C. then poured into 500 g of ice. This heterogeneous mixture wasstirred for 1 h at r.t., filtered, washed with 50 mL H₂ O and theresidue was briefly dried to give 58 g of crude moist6-methyl-2-nitraminopyridine. This solid was carefully added in 1-2 gportions to stirred H₂ SO₄ (70 mL) at 40° C. After complete addition,the reaction mixture was stirred 1 h at 40° C., cooled and poured into500 g of ice. The resulting precipitate was filtered, washed with 50 mLof H₂ O, and air dried to give a yellow solid.

8.5 g of this mixture of 2-amino-6-methyl-3-nitropyridine and2-amino-6-methyl-5-nitropyridine was dissolved in H₂ SO₄ (100 mL) at 0°C. and HNO₃ (2.74 mL, d=1.49) was added drop-wise over 10 min. Aftercomplete addition, the mixture was warmed to 50° C. for 90 min., cooled,then poured onto 200 g of ice. The residue was collected by filtrationand washed with cold H₂ O (2×50 mL) to give2-amino-6-methyl-3,5-dinitropyridine as a yellow solid.

Step 2: Preparation of2-butyl-5-methyl-6-[(1-oxo-pentyl)amino]imidazo[4,5-b]pyridine

The title compound was prepared from2-amino-6-methyl-3,5-dinitropyridine by the method described in Example1, Step 2.

¹ H NMR (CDCl₃, 400 MHz): d 7.79 (s, 1H), 2.88 (t, 2H, J=7.6 Hz), 2.50(s, 3H), 2.45 (t, 2H, J=7.4 Hz), 1.85-1.66 (m, 4H), 1.50-1.34 (m, 4H),0.97 (t, 3H, J=7.4 Hz), 0.95 (t, 3H, J=7.4 Hz).

Step 3: Preparation of2-Butyl-3-[[2'-[[(1,1-dimethyl-ethyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]-methyl]-5-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

The title compound was prepared from2-butyl-5-methyl-6-[(1-oxopentyl)amino]imidazo[4,5-b]-pyridine by themethod described in Example 1, Step 3.

Step 4: Preparation of2-Butyl-3-[[2'-[[(amino)sulfonyl][1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]-pyridine

The title compound was prepared from2-Butyl-3-[[2'-[[(1,1-dimethylethyl)amino]sulfonyl]-[1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[(1-oxopentyl)-amino]-3H-imidazo[4,5-b]pyridineby the method described in Example 1, Step 4.

Step 5: Preparation of2-butyl-3-[[2'-[[(1-oxopentyl)-amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

The title compound was prepared from2-Butyl-3-[[2'-[[(amino)sulfonyl][1,1'-biphenyl]-4-yl]-methyl]-5-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridineand valeryl chloride as described in Example 1, Step 5.

MS (FAB): 619 (M⁺ +1).

EXAMPLE 62-Butyl-3-[[2'-[[(3-cyclopentyl-1-oxopropyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

To a solution of2-butyl-3-[2'-aminosulfonyl]-[1,1'-biphenyl]-4-yl]methyl]-5-metyl-6-[(1-oxopentyl)-amino]-3H-imidazo[4,5-b]pyridine(66 mg, 0.124 mmol) and DMAP (30 mg, 0.248 mmol) in pyridine (1 mL) wasadded 3-cyclopentylpropionyl chloride (200 mL, 1.31 mmol) at rt. Afterthe solution was stirred at rt for 18 h, the reaction was quenched withMeOH. The solution was diluted with EtOAc, washed with brine, and driedover MgSO₄. Concentration followed by flash chromatography (hexanes:EtOAc=1:1, 100% EtOAc, 10% MeOH/EtOAc) afforded2-butyl-3-[[2'-[[(3-cyclopentyl-1-oxopropyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]-methyl]-5-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridineas a solid.

MS (FAB): 658 (M⁺ +1).

EXAMPLE 72-butyl-3-[[2'-[[(3-phenyl-1-oxopropyl)amino]sulfonyl]-[1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-](1-oxopentyl)-amino]-3H-imidazo[4,5-b]pyridine

Step 1: Preparation of2-butyl-3-[2'-aminosulfonyl]-[1,1'-biphenyl]-4-yl]methyl]-5-metyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

To a suspension of 60% NaH (168 mg, 4.21 mmol) in DMF (10 mL) was addeda suspension of2-butyl-5-methyl-6-[(1-oxopentyl)amino]imidazo[4,5-b]-pyridine (1.21 g,4.21 mmol) in DMF (16 mL) in two portions at 0₋₋ C. The mixture wasstirred at 0₋₋ C for 20 min until the gas evolution ceased. To the abovebrown solution was added 4'-bromomethylbiphenyl-2-tert-butylsulfonamide(1.93 g, 5.05 mmol) in DMF (10 mL) dropwise at 0₋₋ C. The solution wasstirred at 0₋₋ C for 30 min and at rt for 18 hrs. After DMF wasevaporated in vacuo, the residue was partitioned between EtOAc andwater. The aqueous layer was extracted with EtOAc (2X), washed withbrine, and dried over anhydrous MgSO₄. Concentration followed by flashchromatography (hexanes :EtOAc=1:1, 100% EtOAc, 10% MeOH/EtOAc) afforded1.36 g of foamy solid. The above solid was dissolved in anhydrous TFAand was stirred at rt for 18 h. After TFA was removed in vacuo, theresidue was dissolved in EtOAc and washed with saturated aq. NaHCO₃. Theaqueous layer was extracted with EtOAc (2X). The combined organic layerwas washed with brine, and dried over anhydrous MgSO₄. Concentrationafforded the title compound as a foamy powder.

Step 2: Preparation of2-butyl-3-[[2'-[[(3-phenyl-1-oxopropyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

A THF (15 mL) solution of hydrocinnamic acid (751 mg, 5 mmol) andcarbonyl-di-imidazole (811 mg, 5 mmol) was refruxed for 3 h. To theabove solution was added a THF (10 mL) solution of DBU (448 mL, 3 mmol)and2-butyl-3-[2'-aminosulfonyl][1,1'-biphenyl]-4-yl]-methyl]-5-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine(533 mg, 1 mmol). The refluxing was continued for 18 h. After cooling,the solution was diluted with EtOAc, washed with 20% aq. citric acid andbrine, and dried over MgSO₄. Concentration followed by flashchromatography (hexanes: EtOAc=1:1, 100% EtOAc, 10% MeOH/EtOAc) afforded2-butyl-3-[[2'-[[(3-phenyl-1-oxopropyl)amino]sulfonyl]-[1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[(1-oxopentyl)-amino]-3H-imidazo[4,5-b]pyridineas a solid.

MS (FAB): 666 (M⁺ +1)

EXAMPLE 82-butyl-3-[[2'-[[[(butylamino)carbonyl]amino]sulfonyl]-[1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[(1-oxopentyl)-amino]-3H-imidazo[4,5-b]pyridine

To a solution of2-butyl-3-[2'-aminosulfonyl]-[1,1'-biphenyl]-4-yl]methyl]-5-metyl-6-[(1-oxopentyl)-amino]-3H-imidazo[4,5-b]pyridine(117 mg, 0.22 mmol) and DBU (100.5 mg, 0.66 mmol) in THF (3 mL) wasadded butylisocyanate (43.6 mg, 0.44 mmol) at rt. After the solution wasstirred at rt for 2 h, the reaction was quenched with MeOH. The solutionwas diluted with EtOAc, washed with 20% aqueous citric acid and brine,and dried over anhydrous MgSO₄. Concentration followed by flashchromatography (100% EtOAc, 10% MeOH/EtOAc, 10% MeOH/CH₂ Cl₂) affordedthe title compound as a solid.

MS (FAB): 633 (M⁺ +1)

EXAMPLE 92-butyl-3-[[2'-[[[(butylamino)carbonyl]amino]sulfonyl]-[1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[[(2-propylamino)carbonyl]amino]-3H-imidazo[4,5-b]pyridine

Step 1: Preparation2-butyl-3-[2'-aminosulfonyl][1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[[(2-propylamino)carbonyl]amino]-3H-imidazo[4.5-b]pyridine

To a solution of2-butyl-3-[2'-(1,1-dimethylethyl)aminosulfonyl][1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine(347 mg, 0.589 mmol) in MeOH (3 mL) was added conc. HCl (2 mL). Afterthe solution was stirred at rt for 42 h, the solution was diluted withEtOAc, neutralized by saturated aq. NaHCO₃, washed with brine, and driedover anhydrous MgSO₄. Concentration followed by flash chromatography(100% EtOAc, 10% MeOH/EtOAc) afforded2-butyl-3-[2'-(1,1-dimethylethyl)aminosulfonyl][1,1'-biphenyl]4-yl]methyl]-5-methyl-6-amino-3H-imidazo[4,5-b]pyridine as a solid. To this solid (100 mg, 0.198 mmol) and DMAP (10 mg,0.08 mmol) in pyridine (2 mL) was added iso-propylisocyanate (24 mL,0.24 mmol). After the solution was stirred at rt for 18 h, the solutionwas quenched with MeOH, and stirred at rt for additional 2 h.Concentration gave a brown glass, which was dissolved in TFA (2 mL) andstirred at rt for 18 h. After TFA was removed in vacuo, the residue wasdissolved in EtOAc and washed with saturated aq. NaHCO₃. The aqueouslayer was extracted with EtOAc (2X). The combined organic layer waswashed with brine, and dried over anhydrous MgSO₄. Concentrationfollowed by flash chromatography (hexanes: EtOAc=1:1, 100% EtOAc, 10%MeOH/EtOAc) afforded the title compound as a foamy powder.

Step 2: Preparation of2-butyl-3-[[2'-[[[(butylamino)-carbonyl]amino]sulfonyl][1,1'-biphenyl]-4-yl]-methyl]-5-methyl-6-[[(2-propylamino)carbonyl]-amino]-3H-imidazo[4,5-b]pyridine

The title compound was prepared from2-butyl-3-[2'-aminosulfonyl][1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[[(2-propylamino)carbonyl]amino]-3H-imidazo-[4,5-b]pyridineand butyl-isocyanate according to the method described in Example 8.

MS (FAB): 634 (M⁺ +1)

Example 105,7-dimethyl-2-propyl-3-[[2'-[[(3-cyclopentyl-1-oxopropyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxobutyl)amino]-3H-imidazo[4,5-b]pyridine

Step 1: Preparation of 2-amino-6-methyl-3,5-dinitropyridine

The title compound is prepared using the method outlined in Example 5step 1 starting with 2-amino-4,6-dimethypyridine in the place of2-amino-6-methylpyridine.

Step 2: Preparation of5,7-dimethyl-2-propyl-6-[(1-oxobutyl)amino]imidazo[4,5-b]pyridine

The title compound is prepared using the method outlined in Example 5step 2 starting with 2-amino-4,6-dimethyl-3,5-dinitropyridine in theplace of 2-amino-6-methylpyridine and butyric acid in the place ofvaleric acid.

Step 3: Preparation of5,7-dimethyl-2-propyl-3-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxobutyl)amino]-3H-imidazo[4,5-b]pyridine

The title compound was prepared from2-propyl-5,7-dimethyl-6-[(1-oxobutyl)amino]imidazo[4,5-b]pyridine by themethod described in Example 5, Steps 3 and 4.

Step 4: Preparation of5,7-dimethyl-2-propyl-3-[[2'-[[(3-cyclopentyl-1-oxopropyl)amino]-sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxobutyl)amino]-3H-imidazo[4,5-b]pyridin

The title compound was prepared from5,7-dimethyl-2-propyl-3-[[2'-(aminosulfonyl)[1,1-biphenyl]-4-yl]methyl]-6-[(1-oxobutyl)amino]-3H-imidazo-[4,5-b]pyridineby the method described in Example 1, Step 5.

FAB MS 644 (M⁺ +1).

EXAMPLE 117-methyl-2-propyl-3-[[2'-[[[(butylamino)carbonyl]amino]-sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxobutyl)-amino]-3H-imidazo[4,5-b]pyridine

Step 1: Preparation of7-methyl-2-propyl-6-[(1-oxobutyl)amino]3H-imidazo[4,5-b]pyridine

The title compound was prepared from2-amino-4-methyl-3,5-dinitropyridine according to method described inExample 1, Step 2 using butyric acid in the place of valeric acid.

Step 2: Preparation of7-methyl-2-propyl-3-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxobutyl)amino]-3H-imidazo[4,5-b]pyridine

The title compound was prepared from7-methyl-2-propyl-6-[(1-oxobutyl)amino]-3H-imidazo[4,5-b]pyridineaccording to method described in Example 1, Step 3.

Step 3: Preparation of7-methyl-2-propyl-3-[[2'-[[[(butylamino)carbonyl]amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxobutyl)amino]-3H-imidazo[4,5-b]pyridine

The title compound was prepared from7-methyl-2-propyl-3-[[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]-methyl]-6-[(1-oxobutyl)amino]-3H-imidazo[4,5-b]pyridineby the method described in Example 3.

FAB MS 643 (M⁺ +39); C₃₂ H₄₀ N₆ SO₄ +K.

EXAMPLE 122-butyl-3-[[2'-[[(benzoyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

The title compound was prepared from2-Butyl-3-[[2'-[[(amino)sulfonyl][1,1'-biphenyl]-4-yl]methyl]-5-methyl-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridineand benzoyl chloride as described in Example 1, Step 5.

MS (FAB): 642 (M⁺ +1)

EXAMPLE 13 Preparation of 4'-bromomethylbiphenyl-2-tert-butylsulfonamide

Step 1: Preparation of 2-bromobenzene(tert-butyl)-sulfonamide

To a stirred solution of 2-bromobenzenesulfonyl chloride (LancasterSynthesis) (2.21 g, 8.65 mmol) in chloroform (40 ml) under nitrogen atroom temperature was added tert-butylamine (Aldrich) (2.30 ml, 21.9mmol). The orange solution was stirred at room temperature for 12 h,then the mixture evaporated to dryness. Flash chromatography (silicagel, 10,15% ethyl acetate-hexane) afforded2-bromobenzene(tert-butyl)sulfonamide as a white solid; ¹ H NMR (300MHz, CDCl₃) δ 8.18 (d, J=8.5 Hz, 1H), 7.73 (d, J=8.5 Hz, 1H), 7.50-7.35(m, 2H), 5.11 (s, 1H), 1.20 (s, 9H).

Step 2: Preparation of p-tolyltrimethyltin

p-Tolylmagnesium bromide solution (Aldrich) (1.0M solution in diethylether) (53 ml, 0.0530 mol) was added dropwise to trimethyltin chloride(6.92 g, 0.0347 mol) in tetrahydrofuran (50 ml) under nitrogen at -10°C. The suspension was allowed to warm slowly to room temperature over 3h then saturated ammonium chloride solution (10 ml) was added followedby sufficient water to dissolve the precipitate. The solution wasextracted three times with diethyl ether-hexane (1:1). The combinedorganic phase was washed with brine, dried (magnesium sulfate) and thesolvents removed in vacuo. Vacuum distillation of the residue afforded acolorless liquid (39°-40° C., 0.1 mm Hg) which was further purified byflash chromatography (silica gel, hexane) to give p-tolyltrimethyltin asa colorless liquid; ¹ H NMR (300 MHz, CDCl₃) δ 7.40 (d, J =7.7 Hz, 2H),7.19 (d, J=7.7 Hz, 2H), 2.34 (s, 3H), 0.30 (s, 9H).

Step 3: Preparation of 4'-methylbiphenyl-2-tert-butylsulfonamide

2-Bromobenzene(tert-butyl)sulfonamide (1.00 g, 3.92 mmol),p-tolyl-trimethyltin (1.95 g, 6.67 mmol),bis(triphenylphosphine)palladium(II) chloride (Aldrich) (165 mg, 0.235mmol) and dimethylformamide (25 ml) were heated with stirring undernitrogen at 90° C. for 5 h. The black suspension was cooled to roomtemperature, then filtered through a pad of celite which was washed withtetrahydrofuran. The colorless filtrate was evaporated to dryness thenchromatographed (silica gel, 8,10% ethyl acetate-hexane) to give4'-methylbiphenyl-2-tert-butylsulfonamide as a white solid; ¹ H NMR (300MHz, CDCl₃) δ 8.16 (d, J =7.9 Hz, 1H), 7.60-7.37 (m, 4H), 7.36-7.24 (m,3H), 3.57 (s, 1H), 2.42 (s, 3H), 0.99 (s, 9H).

Step 4: Preparation of 4'-bromomethylbiphenyl-2-tert-butylsulfonamide

N-Bromosuccinimide (0.387 g, 2.17 mmol), a,a'-azoisobutyronitrile(catalytic), 4'-methylbiphenyl-2-tert-butylsulfonamide (0.55 g, 1.81mmol) and carbon tetrachloride (50 ml) were heated with stirring atreflux for 3 h. After cooling to room temperature the mixture wasfiltered and the filtrate evaporated to dryness. Flash chromatography(silica gel, 10,20% ethyl acetate-hexane) afforded4'-bromomethylbiphenyl-2-tert-butylsulfonamide (77% pure (the remainderof the material was 4'-dibromomethylbiphenyl-2-tert-butylsulfonamide))as a white solid; ¹ H NMR (300 MHz, CDCl₃) δ 8.17 (dd, J=7.5, 1.6 Hz,1H), 7.68-7.45 (m, 6H), 7.31 (dd, J=7.5, 1.6 Hz, 1H), 4.55 (s, 2H), 3.52(s, 1H), 1.00 (s, 9H).

EXAMPLES 14-162-butyl-3-[[2'-[[(3-cyclopentyl-1-oxopropyl)amino]-sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxopentyl)-amino]-7-methyl-3H-imidazo[4,5-b]pyridine2-butyl-3-[[2'-[[(3,5-bis-trifluoromethylbenzoyl)-amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxobutyl)amino]-7-mehtyl-3H-imidazo[4,5-b]pyridine2-propyl-3-[[(4-propylbenzoyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxobutyl)amino]-7-methyl-3H-imidazo[4,5-b]pyridine

The above identified compounds were prepared according to the proceduresoutlined in Example 4, Steps 1 to 5 and Example 11, Step 1.

EXAMPLES 17-192-butyl-3-[[2'-[[(1-oxopentyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine2-butyl-3-[[2'-[[(3,5-bis-trifluoromethylbenzoyl)amino]-sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxopentyl)-amino]-3H-imidazo[4,5-b]pyridine2-butyl-3-[[2'-[[(4-propylbenzoyl)amino]sulfonyl][1,1'-biphenyl]-4-yl]methyl]-6-[(1-oxopentyl)amino]-3H-imidazo[4,5-b]pyridine

The above identified compounds were prepared according to the proceduresoutlined in Example 1.

What is claimed is:
 1. A compound of structural formula I ##STR27## or apharmaceutically acceptable salt thereof wherein: R¹ is:(a) --SO₂NHC(O)R²³, (b) --SO₂ NHC(O)NR⁴ R²³, or (c) --SO₂ NHC(O)N[CH₂ CH₂ ]₂ O;R^(2a) and R^(2b) are independently:(a) H, (b) Cl, Br, I, F, (c) C₁ -C₆-alkyl, unsubstituted or substituted with aryl, furyl, thienyl, pyridyl,C₃ -C₆ -cycloalkyl, F, C₁ -C₆ -alkoxy, polyfluoro-C₁ -C₄ -alkyl,morpholine, pyrrolidine, and --N(R⁴)(R²³), (d) C₁ -C₆ -alkoxy,unsubstituted or substituted with F and polyfluoro-C₁ -C₄ -alkyl, (e) C₁-C₆ -alkoxyalkyl, or (f) aryl;wherein aryl is phenyl or naphthylsubstituted or unsubstituted with one or two substituents selected fromthe group consisting of Cl, Br, I, F, C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy,CF₃, C₁ -C₄ -alkylthio, OH, NH(C₁ -C₄ -alkyl), N(C₁ -C₄ -alkyl)₂, CO₂ H,and CO₂ -C₁ -C₄ -alkyl; R⁴ is:(a) H, (b) aryl, wherein aryl is asdefined above, or (c) C₁ -C₆ -alkyl, substituted or unsubstituted witharyl, furyl, thienyl, pyridyl, C₃ -C₆ -cycloalkyl, and F; R4a is:(a) H,(b) aryl, wherein aryl is as defined above, or (c) C₁ -C₆ -alkyl,substituted or unsubstituted with aryl, furyl, thienyl, pyridyl, C₃ -C₆-cycloalkyl, and F; R⁵ is:(a) --NH₂, (b) --N(R⁴)R²³, (c) --N(R⁴)COR²³,(d) --N(R⁴)(C₃ -C₇ -cycloalkyl), (e) ##STR28## (f) --NHSO₂ CF₃, (g)--NHSO₂ R²³, (h) --NHSO₂ NHR²³, (i) --NHSO₂ NHCOR²³, (j) --NHSO₂ NHSO₂R²³, (k) --N(R⁴)CO₂ R²³, (l) --N(R⁴)CON(R⁴)(R²³), (m) ##STR29## (n)##STR30## n is: 0, 1 or 2; Z is: (a) (CH₂)n, (b) NR⁴, (c) NCOR²³, (d)NCO₂ R²³, (e) NSO₂ R²³, or (f) O; R⁶ is:(a) C₁ -C₉ -alkyl, C₂ -C₆-alkenyl or C₂ -C₆ -alkynyl, which is substituted or unsubstituted witha substituent selected from the group consisting of: aryl as definedabove, C₃ -C₇ -cycloalkyl, Cl, Br, I, F, -CF₂ CF₃, -N(C₁ -C₄ -alkyl)₂,--CF₃, --CF₂ CH₃, C₁ -C₄ -alkoxy; or (b) polyfluoro-C₁ -C₄ -alkyl, (c)C₃ -C₇ -cycloalkyl, unsubstituted or substituted with one or twosubstituents selected from the group consisting of: C₁ -C₄ -alkyl or--CF₃ or (d) C₁ -C₆ -alkyloxy; R^(7a) and R^(7b) are independently:(a)H, (b) --C₁ -C₅ -alkyl, (c) --C₁ -C₅ -polyfluoroalkyl, (d) --C₃ -C₆-cycloalkyl, (e) Cl, Br, I, F, (f) --O--C₁ -C₅ -alkyl, (g) --S--C₁ -C₅-alkyl, (h) --CO₂ R⁴, or (i) --CON(R⁴)(R²³); R²³ is:(a) aryl as definedabove, (b) heteroaryl as defined below, (c) C₃ -C₆ -cycloalkyl, (d) C₁-C₇ -alkyl which can be optionally substituted with a substituent thatis a member selected from the group consisting of aryl as defined above,heteroaryl as defined below, --C₃ -C₇ -cycloalkyl, --O(C₃ -C₇-cycloalkyl) --OH, SH, --C₁ -C₄ -alkyl, --O(C₁ -C₄ -alkyl), --S(C₁ -C₄-alkyl), --CF₃, Cl, Br, F, I, --CO₂ H, --CO₂ --C₁ -C₄ -alkyl, --NH₂,--NH(C₁ -C₄ -alkyl), --NHCOR^(4a), --N(C₁ -C₄ -alkyl)₂, and --OC₆ H₅, or(e) polyfluoro-C₁ -C₄ -alkyl; andwherein heteroaryl is defined as a 5-or 6-membered aromatic ring containing 1, 2 or 3 heteroatoms selectedfrom the group consisting of O, N, and S.
 2. The compound of claim 1 ofstructural Formula II ##STR31## or a pharmaceutically acceptable saltthereof wherein: R¹ is:(a) SO₂ NHCOR²³, or (b) SO₂ NHCONR⁴ R²³ ; R^(2a)is:(a) H, (b) C₁ -C₆ -alkyl or C₁ -C₆ -alkoxy, unsubstituted orsubstituted with polyfluoro-C₁ -C₄ -alkyl; R⁵ is: (a) --N(R⁴)COR²³, (b)--NHSO₂ R²³, (c) --N(R⁴)CO₂ R²³, (d) --N(R⁴)CON(R⁴)R²³,(e) ##STR32## (f)##STR33## (g) ##STR34## n is 0, 1, or 2; Z is: (a) O, (b) NCOR²³, (c)NCO₂ R²³, (d) NSO₂ R²³, or (e) (CH₂)n; and R^(7a) and R^(7b) areindependently:(a) H, (b) C₁ -C₅ -alkyl, or (c) CO₂ R⁴.
 3. The compoundof claim 2 of structural formula: ##STR35## wherein: R^(7a) and R^(7b)are independently: H or CH₃ and all other substituents are as definedTable A below, wherein C₅ H₉ represents cyclopentyl.

                                      TABLE A                                     __________________________________________________________________________    R.sup.6         NR.sup.4a R.sup.23 R.sup.4      R.sup.23a                     __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                     NHEt               H            (CH.sub.2).sub.2 CH.sub.3                                                     3                             (CH.sub.2).sub.3 CH.sub.3                                                                     NHEt               Me           (CH.sub.2).sub.3 CH.sub.3                                                     .                             (CH.sub.2).sub.3 CH.sub.3                                                                     NHEt               H            CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)             (CH.sub.2).sub.3 CH.sub.3                                                                     NEEt               H            CH.sub.2 CH.sub.2                                                             (C.sub..sub.6 H.sub.5)        (CH.sub.2).sub.3 CH.sub.3                                                                     NHEt               Me           CH.sub.2 CH.sub.2                                                             (C.sub..sub.6 H.sub.5)        (CH.sub.2).sub.3 CH.sub.3                                                                     NHEt               H            CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                     NHEt               H            CH.sub.2 O(C.sub..sub.6                                                       H.sub.5)                      (CH.sub.2).sub.3 CH.sub.3                                                                     NHEt               H            CH.sub.2 CH.sub.2                                                             -thiophene-2-yl               (CH.sub.2).sub.3 CH.sub.3                                                                     NHEt               H            C.sub.6 H.sub.5               (CH.sub.2).sub.3 CH.sub.3                                                                     NHEt               H            3,5-dimethylphenyl-1-yl       (CH.sub.2).sub.3 CH.sub.3                                                                     NHEt               H            3,5-bis(trifluoromethyl)-                                                     phenyl-1-yl                   (CH.sub.2).sub.2 CH.sub.3                                                                     NHEt               H            (CH.sub.2).sub.2 CH.sub.3     (CH.sub. 2).sub.2 CH.sub.3                                                                    NHEt               Me           (CH.sub.2).sub.3 CH.sub.3     (CH.sub.2).sub.2 CH.sub.3                                                                     NHEt               H            CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)             (CH.sub.2).sub.2 CH.sub.3                                                                     NHEt               H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.2 CH.sub.3                                                                     NHEt               Me           CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.2 CH.sub.3                                                                     NHEt               H            CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                     NHEt               H            CH.sub.2 O(C.sub.6                                                            H.sub.5)                      (CH.sub.2).sub.2 CH.sub.3                                                                     NHEt               H            CH.sub.2 CH.sub.2                                                             -thiophene-2-yl               (CH.sub.2).sub.2 CH.sub.3                                                                     NHEt               H            C.sub.6 H.sub.5               (CH.sub.2).sub.2 CH.sub.3                                                                     NHEt               H            3,5-dimethylphenyl-1-yl       (CH.sub.2).sub.2 CH.sub.3                                                                     NHEt               H            3,5-bis(trifluoromethyl)-                                                     phenyl-1-yl                   (CH.sub.2).sub.3 CH.sub.3                                                                     NHPr               H            (CH.sub.2).sub.2 CH.sub.3     (CH.sub.2).sub.3 CH.sub.3                                                                     NHPr               Me           (CH.sub.2).sub.3 CH.sub.3     (CH.sub.2).sub.3 CH.sub.3                                                                     NHPr               H            CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)             (CH.sub.2).sub.3 CH.sub.3                                                                     NHPr               H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.3 CH.sub.3                                                                     NHPr               Me           CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.3 CH.sub.3                                                                     NHPr               H            CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                     NHPr               H            CH.sub.2 O(C.sub.6                                                            H.sub.5)                      (CH.sub.2).sub.3 CH.sub.3                                                                     NHPr               H            CH.sub.2 CH.sub.2                                                             -thiophene-2-yl               (CH.sub.2).sub.3 CH.sub.3                                                                     NHPr               H            C.sub.6 H.sub.5               (CH.sub.2).sub.3 CH.sub.3                                                                     NHPr               H            3,5-dimethylphenyl-1-yl       (CH.sub.2).sub.3 CH.sub.3                                                                     NHPr               H            3,5-bis(trifluoromethyl)-                                                     phenyl-1-yl                   (CH.sub.2).sub.2 CH.sub.3                                                                     NHPr               H            (CH.sub.2).sub.2 CH.sub.3     (CH.sub.2).sub.2 CH.sub.3                                                                     NHPr               Me           (CH.sub.2).sub.3 CH.sub.3     (CH.sub.2).sub.2 CH.sub.3                                                                     NHPr               H            (CH.sub.2 CH.sub.2                                                            (C.sub.5 H.sub.9)             (CH.sub.2).sub.2 CH.sub.3                                                                     NHPr               H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.2 CH.sub.3                                                                     NHPr               Me           CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.2 CH.sub.3                                                                     NHPr               H            CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                     NHPr               H            CH.sub.2 O(C.sub.6                                                            H.sub.5)                      (CH.sub.2).sub.2 CH.sub.3                                                                     NHPr               H            CH.sub.2 CH.sub.2                                                             -thiophene-2-yl               (CH.sub.2).sub.2 CH.sub.3                                                                     NHPr               H            C.sub.6 H.sub.5               (CH.sub.2).sub.2 CH.sub.3                                                                     NHPr               H            3,5-dimethylphenyl-1-yl       (CH.sub.2).sub.2 CH.sub.3                                                                     NHPr               H            3,5-bis(trifluoromethyl)-                                                     phenyl-1-yl                   (CH.sub.2).sub.3 CH.sub.3                                                                     N(CH.sub.3)Pr      H            (CH.sub.2).sub.2 CH.sub.3     (CH.sub.2).sub.3 CH.sub.3                                                                     N(CH.sub.3)Pr      Me           (CH.sub.2).sub.3 CH.sub.3     (CH.sub.2).sub.3 CH.sub.3                                                                     N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)             (CH.sub.2).sub.3 CH.sub.3                                                                     N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.3 CH.sub.3                                                                     N(CH.sub.3)Pr      Me           CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.3 CH.sub.3                                                                     N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                     N(CH.sub.3)Pr      H            CH.sub.2 O(C.sub.6                                                            H.sub.5)                      (CH.sub.2).sub.3 CH.sub.3                                                                     N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             -thiophene-2-yl               (CH.sub.2).sub.3 CH.sub. 3                                                                    N(CH.sub.3)Pr      H            C.sub.6 H.sub.5               (CH.sub.2).sub.3 CH.sub.3                                                                     N(CH.sub.3)Pr      H            3,5-dimethylphenyl-1-yl       (CH.sub.2).sub.3 CH.sub.3                                                                     N(CH.sub.3)Pr      H            3,5-bis(trifluoromethyl)-                                                     phenyl-1-yl                   (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)Pr      H            (CH.sub.2).sub.2 CH.sub.3     (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)Pr      Me           (CH.sub.2).sub.3 CH.sub.3     (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)             (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5 )            (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)Pr      Me           CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)Pr      H            CH.sub.2 O(C.sub.6                                                            H.sub.5 )                     (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)Pr      H            CH.sub.2 CH.sub.2                                                             -thiophene-2-yl               (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)Pr      H            C.sub.6 H.sub.5               (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)Pr      H            3,5-dimethylphenyl-1-yl       (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)Pr      H            3,5-bis(trifluoromethyl)-                                                     phenyl-1-yl                   (CH.sub.2).sub.3 CH.sub.3                                                                     NH-iso-Pr          H            (CH.sub.2).sub.3 CH.sub.3     (CH.sub.2).sub.3 CH.sub.3                                                                     NH-iso-Pr          H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.2 CH.sub.3                                                                     NH-iso-Pr          Me           (CH.sub.2).sub.3 CH.sub.3     (CH.sub.2).sub.2 CH.sub.3                                                                     NH-iso-Pr          H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.3 CH.sub.3                                                                     NH-iso-Pr          H            CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2            (CH.sub.2).sub.3 CH.sub.3                                                                     N(CH.sub.3)-iso-Pr H            (CH.sub.2).sub.3 CH.sub.3     (CH.sub.2).sub.3 CH.sub.3                                                                     N(CH.sub.3)-iso-Pr H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)-iso-Pr Me           (CH.sub.2).sub.3 CH.sub.3     (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)-iso-Pr H            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.2 CH.sub.3                                                                     N(CH.sub.3)-iso-Pr H            CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2            (CH.sub.2).sub.2 CH.sub.3                                                                     NH-iso-Pr          H            CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2.           __________________________________________________________________________


4. The compound of claim 2 of structural formula: ##STR36## wherein:R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined in Table B below:

                                      TABLE B                                     __________________________________________________________________________    R.sup.6                NR.sup.4a R.sup.23        NR.sup.4 R.sup.23a           __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                            NHEt                      NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                            NHEt                      NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.3 CH.sub.3                                                                            NHEt                      NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                            NHEt                      NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                            NHEt                      N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                            NHEt                      NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                            NHEt                      NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.2 CH.sub.3                                                                            NHEt                      NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                            NHEt                      NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.2 CH.sub.3                                                                            NHEt                      N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                            NHPr                      NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                            NHPr                      NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.3 CH.sub.3                                                                            NHPr                      NH(CH.sub.2).sub.2                                                            CH(CH.sub. 3).sub.2          (CH.sub.2).sub.3 CH.sub.3                                                                            NHPr                      NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                            NHPr                      N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                            NHPr                      NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                            NHPr                      NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.2 CH.sub.3                                                                            NHPr                      NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                            NHPr                      NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.2 CH.sub.3                                                                            NHPr                      N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                            NH-iso-Pr                 NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                            NH-iso-Pr                 NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.3 CH.sub.3                                                                            NH-iso-Pr                 NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                            NH-iso-Pr                 NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                            NH-iso-Pr                 N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                            NH-iso-Pr                 NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                            NH-iso-Pr                 NHCH.sub.2 CH(CH.sub.3).s                                                     ub. 2                        (CH.sub.2).sub.2 CH.sub.3                                                                            NH-iso-Pr                 NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                            NH-iso-Pr                 NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.2 CH.sub.3                                                                            NH-iso-Pr                 N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.3 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.3 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NH(CH.sub.2).sub.3                                                            CH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NHCH.sub.2 CH(CH.sub.3).s                                                     ub.2                         (CH.sub.2).sub.2 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        NHCH.sub.2 (C.sub.6                                                           H.sub.5)                     (CH.sub.2).sub.2 CH.sub.3                                                                            N(CH.sub.3)-iso-Pr        N(CH.sub. 3)CH.sub.2                                                          (C.sub.6 H.sub.5).           __________________________________________________________________________


5. The compound of claim 2 of structural formula: ##STR37## wherein:R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined in Table C below, wherein C₅ H₉ and C₆ H₁₁represent cylcopentyl and cyclohexyl, respectively:

                                      TABLE C                                     __________________________________________________________________________    R.sup.6          R.sup.23         R.sup.4       R.sup.23a                     __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             (CH.sub.2).sub.2 CH.sub.3                                                     5                             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             (CH.sub.2).sub.3 CH.sub.3                                                     .                             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      Me            (CH.sub.2).sub.3 CH.sub.3     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             (CH.sub.2).sub.4 CH.sub.3     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      Me            (CH.sub.2).sub.4 CH.sub.3     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             (CH.sub.2).sub.5 CH.sub.3     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             (CH.sub.3).sub.2              (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH(CH.sub.3)CH(CH                                                    .sub.3).sub.2                 (CH.sub.2).sub. 3 CH.sub.3                                                                     (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 (C.sub.5                                                             H.sub.9)                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 (C.sub.6                                                             H.sub.11)                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.11)            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 (C.sub.6                                                             H.sub.5)                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      Me            CH.sub.2 (C.sub.6                                                             H.sub.5)                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      Me            CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH(CH.sub.3)CH.sub.2                                                          CH.sub.3                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH(CH.sub.3)CH.sub. 2                                                         CH.sub.2 CH.sub.3             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             C(CH.sub.3).sub.2                                                             CH.sub.2 CH.sub.3             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             C(CH.sub.3).sub.2                                                             CH.sub.2 CH.sub.2                                                             CH.sub.3                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CHC(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CHC(CH.sub.3).sub                                                    .2                            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             OCH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             O(C.sub.6 H.sub.5)            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             OCH.sub.2 CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 OCH.sub.2                                                            CH.sub.3                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 OCH.sub.2                                                            (C.sub.6 H.sub.5)             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 OCH(CH.sub.3).sub                                                    .2                            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 OCH.sub.2                                                            CH.sub.2 CH.sub.3             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 OCH.sub.2                                                            CH(CH.sub.3).sub.2            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 O(C.sub.6                                                            H.sub.5)                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 O(C.sub.5                                                            H.sub.9)                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 OCH.sub.2                                                            CH.sub.2 OCH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             -furan-2-yl                   (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             -furan-3-yl                   (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             -thiophene-2-yl               (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             -thiophene-3-yl               (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             cyclopropane                  (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             2,2-dimethylcyclo-                                                            propane-1-yl                  (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             C.sub.5 H.sub.9               (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             C.sub.6 H.sub.11              (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             C.sub.6 H.sub.5               (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             2-CH.sub.3 --C.sub.6                                                          H.sub.4                       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             2-CH.sub.3 --C.sub.6                                                          H.sub.4                       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             2-CF.sub.3 --C.sub.6                                                          H.sub.4                       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             3-CH.sub.3 --C.sub.6                                                          H.sub.4                       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             3-CH.sub.2 CH.sub.2                                                           CH.sub.3 --C.sub.6                                                            H.sub.4                       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             3-CF.sub.3 --C.sub.6                                                          H.sub.4                       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             3,5-dimethylphenyl-1-yl       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             3,5 bis(trifluoro-                                                            methyl)phenyl-1-yl            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             furan-2-yl                    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2 .sub.3 CH.sub.3                                                                      H             furan-3-yl                    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             thiophene-2-yl                (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             thiophene-3-yl                (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             3-methylthiophene-2-yl        (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             3-chlorothiophene-2-yl        (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             3-bromothiophene-2-yl         (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             3-methylfuran-2-yl            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             3-chlorofuran-2-yl            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             3-bromofuran-2-yl             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             4-propylphenyl                (CH.sub.2).sub. 2 CH.sub.3                                                                     (CH.sub.2).sub.2 CH.sub.3                                                                      H             (CH.sub.2).sub.2 CH.sub.3                                                     2                             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             Butyl                         (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      Me            Butyl                         (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             .sup.n Pentyl                 (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             .sup.n Hexyl                  (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH(CH.sub.3).sub.                                                    2                             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH(CH.sub.3)CH(CH                                                    .sub.3).sub.2                 (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 (C.sub.5                                                             H.sub.9)                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9)             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      Me            CH.sub.2 CH.sub.2                                                             (C.sub.5 H.sub.9 )            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 (C.sub.6                                                             H.sub.11)                     (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.11)            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 (C.sub.6                                                             H.sub.5)                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             (C.sub.6 H.sub.5)             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH(CH.sub.3)CH.sub.2                                                          CH.sub.3                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH(CH.sub.3)CH.sub.2                                                          CH.sub.2 CH.sub.3             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             C(CH.sub.3).sub.2                                                             CH.sub.2 CH.sub.3             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             C(CH.sub.3).sub.2                                                             CH.sub.2 CH.sub.2                                                             CH.sub.3                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CHC(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.                                                                       2 CHC(CH.sub.3).sub.2         (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             OCH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             O(C.sub.6 H.sub.5)            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             OCH.sub.2 CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             OCH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 OCH.sub.2                                                            CH.sub.3                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 OCH.sub.2                                                            (C.sub.6 H.sub.5)             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 OCH(CH.sub.3).sub                                                    .2                            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 OCH.sub.2                                                            CH.sub.2 CH.sub.3             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 OCH.sub.2                                                            CH(CH.sub.3).sub.2            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 O(C.sub.6                                                            H.sub.5)                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 O(C.sub.5                                                            H.sub.9)                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 OCH.sub.2                                                            CH.sub.2 OCH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             -furan-2-yl                   (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             -furan-3-yl                   (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             -thiophene-2-yl               (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             CH.sub.2 CH.sub.2                                                             -thiophene-3-yl               (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             cyclopropane                  (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             2,2-dimethylcyclo-                                                            propane-1-yl                  (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             C.sub.5 H.sub.9               (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             C.sub.6 H.sub.11              (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub. 3                                                                     H             C.sub.6 H.sub.5               (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             2-CH.sub.3 --C.sub.6                                                          H.sub.4                       (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             2-CH.sub.3 --C.sub.6                                                          H.sub.4                       (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             2-CF.sub.3 --C.sub.6                                                          H.sub.4                       (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             3-CH.sub.3 --C.sub.6                                                          H.sub.4                       (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             3-CH.sub.2 CH.sub.2                                                           CH.sub.3 --C.sub.6                                                            H.sub..sub.4                  (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             3-CF.sub.3 --C.sub.6                                                          H.sub.4                       (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             3-CF.sub.3 -5-CF.sub.3                                                        --C.sub.6 H.sub.3             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             furan-2-yl                    (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             furan-3-yl                    (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             thiophene-2-yl                (CH.sub.2).sub.2 CH.sub. 3                                                                     (CH.sub.2).sub.2 CH.sub.3                                                                      H             thiophene-3-yl                (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             3-methylthiophene-2-yl        (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             3-chlorothiophene-2-yl        (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             3-bromothiophene-2-yl         (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             3-methylfuran-2-yl            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             3-chlorofuran-2-yl            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             3-bromofuran-2-yl             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             4-propylphenyl.               __________________________________________________________________________


6. The compound of claim 2 of structural formula: ##STR38## wherein:R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined in Table D below, wherein C₅ H₉ and C₆ H₁₁represent cyclopentyl and cyclohexyl, respectively:

                                      TABLE D                                     __________________________________________________________________________    R.sup.6          R.sup.23         R.sup.4a      NR.sup.4 R.sup.23a            __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            CH.sub.3                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH(CH.sub.2).sub.3                                                            CH.sub.3                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH(CH.sub.2).sub.4                                                            CH.sub.3                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NHCH.sub.2 CH(CH.sub.3).su                                                    b.2                           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NHC.sub.5 H.sub.9             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NHC.sub.6 H.sub.11            (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NHC.sub.6 H.sub.5             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH(3,5-dimethylphen-1-yl)                                                     .                             (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NHCH.sub.2 (C.sub. 6                                                          H.sub.5)                      (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NHCH.sub.2 -thiophene-2-yl    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NHCH.sub.2 -thiophene-3-yl    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            OCH.sub.3                     (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            OCH(CH.sub.3).sub.2           (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             morpholine-1-yl               (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             N(CH.sub.3)(CH.sub.2).sub.                                                    3 CH.sub.3                    (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             N(CH.sub.3)C.sub.6                                                            H.sub.5                       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                      H             N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5)             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            CH.sub.3                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NH(CH.sub.2).sub.3                                                            CH.sub.3                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub. 2 CH.sub.3                                                                     H             NH(CH.sub.2).sub.4                                                            CH.sub.3                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHCH.sub.2 CH(CH.sub.3).su                                                    b.2                           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            CH(CH.sub.3).sub.2            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHC.sub.5 H.sub.9             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHC.sub.6 H.sub.11            (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHC.sub.6 H.sub.5             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NH(3,5-dimethylphen-1-yl)                                                     O                             (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHCH.sub.2 (C.sub.6                                                           H.sub.5)                      (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHCH.sub.2 -thiophene-2-yl    (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NHCH.sub.2 -thiophene-3-yl    (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NH(CH.sub.2).sub.2                                                            OCH.sub.3                     (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             NH(CH.sub. 2).sub.2                                                           OCH(CH.sub.3).sub.2           (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             morpholine-1-yl               (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             N(CH.sub.3)(CH.sub.2).sub.                                                    2 CH.sub.3                    (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             N(CH.sub.3)C.sub.6                                                            H.sub.5                       (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.2 CH.sub.3                                                                      H             N(CH.sub.3)CH.sub.2                                                           (C.sub.6 H.sub.5).            __________________________________________________________________________


7. The compound of claim 2 of structural formula: ##STR39## wherein thesubstituents are as define in Table E below:

                                      TABLE E                                     __________________________________________________________________________    R.sup.6             NR.sup.4a R.sup.23    R.sup.7a        R.sup.7b            __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                         NHEt                  H               H                   (CH.sub.2).sub.3 CH.sub.3                                                                         NHEt                  H               CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                         NHEt                  CH.sub.3        H                   (CH.sub.2).sub.3 CH.sub.3                                                                         NHEt                  CH.sub.3        CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         NHEt                  H               H                   (CH.sub.2).sub.2 CH.sub.3                                                                         NHEt                  H               CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         NHEt                  CH.sub.3        H                   (CH.sub.2).sub.2 CH.sub.3                                                                         NHEt                  CH.sub.3        CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                         NHPr                  H               H                   (CH.sub.2).sub.3 CH.sub.3                                                                         NHPr                  H               CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                         NHPr                  CH.sub.3        H                   (CH.sub.2).sub.3 CH.sub.3                                                                         NHPr                  CH.sub.3        CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         NHPr                  H               H                   (CH.sub.2).sub.2 CH.sub.3                                                                         NHPr                  H               CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         NHPr                  CH.sub.3        H                   (CH.sub.2).sub.2 CH.sub.3                                                                         NHPr                  CH.sub.3        CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                         NH-iso Pr             H               H                   (CH.sub.2).sub.3 CH.sub.3                                                                         NH-iso Pr             H               CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                         NH-iso-Pr             CH.sub.3        H                   (CH.sub.2).sub.3 CH.sub.3                                                                         NH-iso-Pr             CH.sub.3        CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         NH-iso-Pr             H               H                   (CH.sub.2).sub.2 CH.sub.3                                                                         NH-iso-Pr             H               CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         NH-iso-Pr             CH.sub.3        H                   (CH.sub.2).sub.2 CH.sub.3                                                                         NH-iso-Pr             CH.sub.3        CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr    H               H                   (CH.sub.2).sub.3 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr    H               CH.sub.3            (CH.sub.2).sub.3 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr    CH.sub.3        H                   (CH.sub.2).sub.3 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr    CH.sub.3        CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr    H               H                   (CH.sub.2).sub.2 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr    H               CH.sub.3            (CH.sub.2).sub.2 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr    CH.sub.3        H                   (CH.sub.2).sub.2 CH.sub.3                                                                         N(CH.sub.3)-iso-Pr    CH.sub.3        CH.sub.3.           __________________________________________________________________________


8. The compound of claim 2 of structural formula: ##STR40## wherein:R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined in Table F below:

                                      TABLE F                                     __________________________________________________________________________    R.sup.6            R.sup.23        R.sup.4         R.sup.23a                  __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                        Bu              H               (CH.sub.2).sub.3                                                              CH.sub.3                   (CH.sub.2).sub.3 CH.sub.3                                                                        Bu              H               CH.sub.2 CH.sub.2                                                             C.sub.6 H.sub.5            (CH.sub.2).sub.3 CH.sub.3                                                                        Bu              Me              (CH.sub.2).sub.3                                                              CH.sub.3                   (CH.sub.2).sub.3 CH.sub.3                                                                        Bu              H               CH.sub.2 CH.sub.2                                                             C.sub.6 H.sub.5            (CH.sub.2).sub.3 CH.sub.3                                                                        Bu              H               CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2         (CH.sub.2).sub.2 CH.sub.3                                                                        Bu              H               (CH.sub.2).sub.3                                                              CH.sub.3                   (CH.sub.2).sub.2 CH.sub.3                                                                        Bu              H               CH.sub.2 CH.sub.2                                                             C.sub.6 H.sub.5            (CH.sub.2).sub.2 CH.sub.3                                                                        Bu              Me              (CH.sub.2).sub.2                                                              CH.sub.3                   (CH.sub.2).sub.2 CH.sub.3                                                                        Bu              H               CH.sub.2 CH.sub.2                                                             C.sub.6 H.sub.5            (CH.sub.2).sub.2 CH.sub.3                                                                        Bu              H               CH.sub.2 CH.sub.2                                                             CH(CH.sub.3).sub.2.        __________________________________________________________________________


9. The compound of claim 2 of structural formula III ##STR41## or apharmaceutically acceptable salt thereof, wherein: R¹ is: --SO₂ NHCOR²³or --SO₂ NHCONR⁴ R²³ ;R^(2a) is: H, --CH₃, --CH₂ CH₃, --(CH₂)₂ CH₃,--CH(CH₃)₂, --CH₂ CH(CH₃)₂, --OCH₂ CH₃, or --OCH₂ CF₃ ; R⁵is:--N(R⁴)COR²³, --NHSO₂ R²³, --N(R⁴)CO₂ R²³, --N(R⁴)CON(R⁴)R²³, or##STR42## R⁶ is: ethyl, propyl, butyl, cyclopropyl, ethyloxy orpropyloxy.
 10. The compound of claim 9 of structural formula ##STR43##wherein: R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined in Table G below, wherein C₅ H₉ representscyclopentyl:

                                      TABLE G                                     __________________________________________________________________________    R.sup.6           R.sup.23         R.sup.23a             R.sup.2a             __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                           Pr                   (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                      CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                 Pr                   (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                      CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.3                                                                Pr                   (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                      C.sub.6 H.sub.5       Pr                   (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                           Et                   (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                      CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                 Et                   (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                      CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.3                                                                Et                   (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                      C.sub.6 H.sub.5       Et                   (CH.sub.2).sub.2 CH.sub.3                                                                       (CH.sub.2).sub.2 CH.sub.3                                                                      CH.sub.2 CH.sub.2 (C.sub.6 H.sub.5)                                                                 Pr                   (CH.sub.2).sub.2 CH.sub.3                                                                       (CH.sub.2).sub.2 CH.sub.3                                                                      CH.sub.2 CH.sub.2 (C.sub.6 H.sub.5)                                                                 Et                   (CH.sub.2).sub.2 CH.sub.3                                                                       (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                           Pr                   (CH.sub.2).sub.2 CH.sub.3                                                                       (CH.sub.2).sub.2 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                           Et                   (CH.sub.2).sub.2 CH.sub.3                                                                       (CH.sub.2).sub.2 CH.sub.3                                                                      C.sub.6 H.sub.5       Pr                   (CH.sub.2).sub.2 CH.sub.3                                                                       (CH.sub.2).sub.2 CH.sub.3                                                                      C.sub.6 H.sub.5       Et                   (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                      CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.3                                                                iso-Bu               (CH.sub.2).sub.3 CH.sub.3                                                                       (CH.sub.2).sub.3 CH.sub.3                                                                      (CH.sub.2).sub.3 CH.sub.3                                                                           iso-Bu.              __________________________________________________________________________


11. The compound of claim 9 of structural formula ##STR44## wherein:R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined in Table H below:

                                      TABLE H                                     __________________________________________________________________________    R.sup.6            R.sup.23           R.sup.23a          R.sup.2a             __________________________________________________________________________    (CH.sub.2).sub.3 CH.sub.3                                                                        (CH.sub.2).sub.3 CH.sub.3                                                                        (CH.sub.2).sub.3 CH.sub.3                                                                        Pr                   (CH.sub.2).sub.2 CH.sub.3                                                                        (CH.sub.2).sub.2 CH.sub.3                                                                        (CH.sub.2).sub.3 CH.sub.3                                                                        Pr                   (CH.sub.2).sub.3 CH.sub.3                                                                        (CH.sub.2).sub.3 CH.sub.3                                                                        (CH.sub.2).sub.3 CH.sub.3                                                                        Et                   (CH.sub.2).sub.2 CH.sub.3                                                                        (CH.sub.2).sub.2 CH.sub.3                                                                        (CH.sub.2).sub.3 CH.sub.3                                                                        Et                   (CH.sub.2).sub.2 CH.sub.3                                                                        (CH.sub.2).sub.2 CH.sub.3                                                                        (CH.sub.2).sub.3 CH.sub.3                                                                        iso-Bu.              __________________________________________________________________________


12. The compound of claim 9 of structural formula ##STR45## wherein:R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined Table I below, wherein C₅ H₉ representscyclopentyl:

                                      TABLE I                                     __________________________________________________________________________    R.sup.6            R.sup.23         R.sup.23a            R.sup.2a             __________________________________________________________________________    CH.sub.2 CH.sub.3  Et               (CH.sub.2).sub.3 CH.sub.3                                                                          Pr                   CH.sub.2 CH.sub.3  CH.sub.3         CH.sub.2 CH.sub.2 C.sub.5 H.sub.9)                                                                 Pr                   (CH.sub.2).sub.3 CH.sub.3                                                                        iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                          Pr                   CH.sub.2 CH.sub.3  iso-Pr           CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                Pr                   (CH.sub.2).sub.2 CH.sub.3                                                                        iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                          Pr                   CH.sub.2 CH.sub.3  Et               (CH.sub.2).sub.3 CH.sub.3                                                                          Et                   CH.sub.2 CH.sub.3  CH.sub.3         CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                Et                   (CH.sub.2).sub.3 CH.sub.3                                                                        iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                          Et                   CH.sub.2 CH.sub.3  iso-Pr           CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                Et                   (CH.sub.2).sub.2 CH.sub.3                                                                        iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                          Et                   CH.sub.2 CH.sub.3  Et               (CH.sub.2).sub.3 CH.sub.3                                                                          iso-Bu               CH.sub.2 CH.sub.3  CH.sub.3         CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                iso-Bu               (CH.sub.2).sub.3 CH.sub.3                                                                        iso-Pr           (CH.sub.2).sub. 3 CH.sub.3                                                                         iso-Bu               CH.sub.2 CH.sub.3  iso-Pr           CH.sub.2 CH.sub.2 (C.sub.5 H.sub.9)                                                                iso-Bu               (CH.sub.2).sub.2 CH.sub.3                                                                        iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                          iso-Bu.              __________________________________________________________________________


13. The compound of claim 9 of structural formula ##STR46## wherein:R^(7a) and R^(7b) are independently: H or CH₃, and all othersubstitutents are as defined in Table J below:

                                      TABLE J                                     __________________________________________________________________________    R.sup.6             R.sup.23         R.sup.23a           R.sup.2a             __________________________________________________________________________    (CH.sub.2).sub.2 CH.sub.3                                                                         Et               (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                   (CH.sub.2).sub.2 CH.sub.3                                                                         Et               (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                   CH.sub.2 CH.sub.3   Et               (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                   CH.sub.2 CH.sub.3   CH.sub.3         (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                   (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                   CH.sub.2 CH.sub.3   iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                   (CH.sub.2).sub.2 CH.sub.3                                                                         iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                         Pr                   (CH.sub.2).sub.2 CH.sub.3                                                                         Et               (CH.sub.2).sub.3 CH.sub.3                                                                         Et                   (CH.sub.2).sub.3 CH.sub.3                                                                         Et               (CH.sub.2).sub.3 CH.sub.3                                                                         Et                   CH.sub.2 CH.sub.3   Et               (CH.sub.2).sub.3 CH.sub.3                                                                         Et                   CH.sub.2 CH.sub.3   CH.sub.3         (CH.sub.2).sub.3 CH.sub.3                                                                         Et                   (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                         Et                   CH.sub.2 CH.sub.3   iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                         Et                   (CH.sub.2).sub.2 CH.sub.3                                                                         iso-Pr           (CH.sub. 2).sub.3 CH.sub.3                                                                        Et                   (CH.sub.2).sub.2 CH.sub.3                                                                         Et               (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu               (CH.sub.2).sub.3 CH.sub.3                                                                         Et               (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu               CH.sub.2 CH.sub.3   Et               (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu               CH.sub.2 CH.sub.3   CH.sub.3         (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu               (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu               CH.sub.2 CH.sub.3   iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu               (CH.sub.2).sub.2 CH.sub.3                                                                         iso-Pr           (CH.sub.2).sub.3 CH.sub.3                                                                         iso-Bu.              __________________________________________________________________________


14. A pharmaceutical composition useful in the treatment of hypertensionwhich comprises a pharmaceutically acceptable carrier and atherapeutically effective amount of a compound of claim
 1. 15. A methodof treating hypertension which comprises administering to a patient inneed of such treatment a therapeutically effective amount of a compoundof claim
 1. 16. An ophthalmological formulation for the treatment ofocular hypertension comprising an ophthalmologically acceptable carrierand an effective ocular antihypertensive amount of a compound ofclaim
 1. 17. A method of treating ocular hypertension comprising topicalocular administration to a patient in need of such treatment of aneffective ocular antihypertensive amount of a compound of claim
 1. 18. Amethod of treating cognitive dysfunction, anxiety, or depressioncomprising administering to a patient in need of such treatment, atherapeutically effective amount of a compound of claim 1.